Andrew Leask

Summary

Affiliation: University of Western Ontario
Country: Canada

Publications

  1. ncbi Sonic advance: CCN1 regulates sonic hedgehog in pancreatic cancer
    Andrew Leask
    Department of Dentistry, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 7:61-2. 2013
  2. ncbi Focal adhesion kinase and reactive oxygen species contribute to the persistent fibrotic phenotype of lesional scleroderma fibroblasts
    Xu Shi-Wen
    Centre for Rheumatology, University College London Royal Free Campus, London, UK
    Rheumatology (Oxford) 51:2146-54. 2012
  3. ncbi Trial by CCN2: a standardized test for fibroproliferative disease?
    Andrew Leask
    Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:87-8. 2009
  4. ncbi What's in an intron? CCN1 mRNA splicing in cancer
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:151-2. 2009
  5. ncbi Death of a tumor: targeting CCN in pancreatic cancer
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:159-60. 2009
  6. ncbi Regulation of CCN2 mRNA expression and promoter activity in activated hepatic stellate cells
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, Ontario, N6A 5C1, Canada
    J Cell Commun Signal 2:49-56. 2008
  7. ncbi Yin and Yang: CCN3 inhibits the pro-fibrotic effects of CCN2
    Andrew Leask
    Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 3:161-2. 2009
  8. ncbi CCN2 YAPs at cancer
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 2:47-8. 2008
  9. ncbi The Starbuck stops here: it's a Smad world
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 2:1-2. 2008
  10. ncbi Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease?
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 3:89-94. 2009

Collaborators

Detail Information

Publications96

  1. ncbi Sonic advance: CCN1 regulates sonic hedgehog in pancreatic cancer
    Andrew Leask
    Department of Dentistry, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 7:61-2. 2013
    ..CCN1 activity was mediated, at least in part, through altering proteosome activity. These results suggest that CCN1 may be an ideal target for treating PDAC...
  2. ncbi Focal adhesion kinase and reactive oxygen species contribute to the persistent fibrotic phenotype of lesional scleroderma fibroblasts
    Xu Shi-Wen
    Centre for Rheumatology, University College London Royal Free Campus, London, UK
    Rheumatology (Oxford) 51:2146-54. 2012
    ..We aim to identify the precise contribution of adhesive signalling, which requires integrin-mediated activation of focal adhesion kinase (FAK)/src, to fibrogenic gene expression in normal and fibrotic SSc fibroblasts...
  3. ncbi Trial by CCN2: a standardized test for fibroproliferative disease?
    Andrew Leask
    Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:87-8. 2009
    ..The relative levels of vascular endothelial growth factor (VEGF) and CCN2 (connective tissue growth factor [CTGF]) were examined in proliferative diabetic retinopathy (PDR). This paper is the subject of this commentary...
  4. ncbi What's in an intron? CCN1 mRNA splicing in cancer
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:151-2. 2009
    ..In cancers, or upon hypoxia, intron 3 is removed resulting in the appearance of CCN1 protein. The significance of this paper is discussed...
  5. ncbi Death of a tumor: targeting CCN in pancreatic cancer
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:159-60. 2009
    ..Cancer Res 69:775-784, 2009) has used shRNA knockdown of CCN2 to illustrate that CCN2 contributes to growth of pancreatic tumor cells, both in vitro and in vivo. This report briefly summarizes these findings...
  6. ncbi Regulation of CCN2 mRNA expression and promoter activity in activated hepatic stellate cells
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, Ontario, N6A 5C1, Canada
    J Cell Commun Signal 2:49-56. 2008
    ....
  7. ncbi Yin and Yang: CCN3 inhibits the pro-fibrotic effects of CCN2
    Andrew Leask
    Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 3:161-2. 2009
    ..174:1725-34, 2009) illustrates that CCN3 (nov) antagonizes the fibrogenic effects of CCN2. This paper, the subject of this commentary, raises the intriguing possibility that CCN3 may be used as a novel anti-fibrotic therapy...
  8. ncbi CCN2 YAPs at cancer
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 2:47-8. 2008
    ..These data confirm the role of CCN2 as a key oncogenic mediator. This report briefly summarizes these findings...
  9. ncbi The Starbuck stops here: it's a Smad world
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 2:1-2. 2008
    ..A recent study by Gressner and colleagues suggested caffeine may block CCN2 expression in hepatic cells. This commentary briefly summarizes these observations...
  10. ncbi Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease?
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 3:89-94. 2009
    ..That CCN2 should be considered a novel and informative surrogate clinical bio-marker for fibroproliferative disease is discussed...
  11. ncbi Egr-ly awaiting a "personalized medicine" approach to treat scleroderma
    Andrew Leask
    Departments of Dentistry and Physiology and Pharmacology, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 6:111-3. 2012
    ..Moreover, targeting IL-13 expression/activity might be a novel therapeutic strategy to target the inflammation leading to "localized" scleroderma...
  12. ncbi CCN3: a novel anti-fibrotic treatment in end-stage renal disease?
    Andrew Leask
    Departments of Dentistry and Physiology and Pharmacology, Dental Sciences Building, Western University, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 6:115-6. 2012
    ..Thus CCN3 protein may represent a novel therapeutic approach to help repair glomerular endothelial damage and mesangioproliferative changes and hence prevent renal failure, glomerulosclerosis and tubulointerstitial fibrosis...
  13. ncbi Emerging targets for the treatment of scleroderma
    Andrew Leask
    University of Western Ontario, Schulich School of Medicine and Dentistry, Departments of Dentistry and Physiology and Pharmacology, Dental Sciences Building, London, ON N6A 5C1, Canada
    Expert Opin Emerg Drugs 17:173-9. 2012
    ..Indeed, drugs currently approved for other rheumatic disease might also be used to treat scleroderma patients bearing an 'inflammatory' gene expression profile...
  14. ncbi Toward personalized medicine in scleroderma: classification of scleroderma patients into stable "inflammatory" and "fibrotic" subgroups
    Andrew Leask
    Department of Dentistry, Dental Sciences Building, Western University, London, Ontario, Canada
    J Invest Dermatol 132:1329-31. 2012
    ..The inflammatory patients might be treated with anti-inflammatory agents, whereas fibroproliferative patients might be treated with antifibrotic agents...
  15. ncbi Loss of PPARγ expression by fibroblasts enhances dermal wound closure
    Wei Sha
    Department of Dentistry, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Bldg, London, ON, N6A 5C1, Canada
    Fibrogenesis Tissue Repair 5:5. 2012
    ..abstract:..
  16. ncbi MEK/ERK inhibitors: proof-of-concept studies in lung fibrosis
    Andrew Leask
    Departments of Dentistry and Physiology and Pharmacology, University of Western Ontario, Dental Sciences Building, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 6:59-60. 2012
    ..Thus MEK inhibition could be a valuable method to treat lung fibrosis...
  17. ncbi Sp1king out cancer (....and fibrosis?)
    Andrew Leask
    Department of Dentistry, University of Western Ontario, London, ON, Canada, NGA 5C1
    J Cell Commun Signal 6:61-2. 2012
    ..Given that Sp1 proteins also promote expression of profibrotic genes such as collagen type I and CCN2, it is possible that this combinatorial approach may be taken in the future to block not only cancer but also fibrosis...
  18. ncbi A sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON N6A 5C1 Canada
    J Cell Commun Signal 4:71-2. 2010
    ..Thus the utility of anti-CCN1 therapy in cancer needs to be carefully considered in light of these divergent results. The significance of this paper is discussed...
  19. ncbi Getting to the heart of the matter: CCN2 plays a role in cardiomyocyte hypertrophy
    Andrew Leask
    Division of Oral Biology and Department of Physiology and Pharmacology, University of Western Ontario, Dental Sciences Building, London, ON N6A 5C1 Canada
    J Cell Commun Signal 4:73-4. 2010
    ..CCN2 acted via the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy in diabetes...
  20. ncbi Thrombin-induced CCN2 expression as a target for anti-fibrotic therapy in scleroderma
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology, Department of Dentistry, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON Canada N6A 5C1
    J Cell Commun Signal 4:111-2. 2010
    ..These results strongly suggest that dabigatran may be a potential antifibrotic drug for the treatment of fibrosing diseases such as scleroderma...
  21. ncbi Pericytes display increased CCN2 expression upon culturing
    Xu Shiwen
    Centre for Rheumatology, University College London Royal Free Campus, Rowland Hill Street, London, UK, NW3 2PF
    J Cell Commun Signal 3:61-4. 2009
    ..These results indicate that, in principle, pericytes have the capacity to become fibroblast-like and that pericytes may contribute to the population of fibroblasts in a healed wound...
  22. ncbi Connective tissue growth factor is induced in bleomycin-induced skin scleroderma
    Shangxi Liu
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON N6A 5C1 Canada
    J Cell Commun Signal 4:25-30. 2010
    ..Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction. Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma...
  23. ncbi Wnt 10b activates the CCN2 promoter in NIH 3T3 fibroblasts through the Smad response element
    Shaoqiong Chen
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:57-9. 2009
    ..These results suggest that Wnts may cross-talk with the Smad signaling pathway to induce fibrotic responses in fibroblasts...
  24. ncbi Thrombospondin 1 in hypoxia-conditioned media blocks the growth of human microvascular endothelial cells and is increased in systemic sclerosis tissues
    Luke Morgan-Rowe
    Centre for Rheumatology Research and Connective Tissue Diseases, The Royal Free Hospital Campus, University College London, Pond Street, London NW3 2QG, UK
    Fibrogenesis Tissue Repair 4:13. 2011
    ..abstract:..
  25. ncbi Src kinase inhibition promotes the chondrocyte phenotype
    Laura Bursell
    Department of Physiology and Pharmacology, Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1
    Arthritis Res Ther 9:R105. 2007
    ..Strategies to block Src activity might therefore be useful both in tissue engineering of cartilage and in the maintenance of the chondrocyte phenotype in diseases such as osteoarthritis...
  26. ncbi The induction of CCN2 by TGFbeta1 involves Ets-1
    Jonathan P van Beek
    CIHR Group in Skeletal Development and Remodeling, Schulich School of Medicine and Dentistry, Dental Sciences Building, The University of Western Ontario, London, ON N6A 5C1, Canada
    Arthritis Res Ther 8:R36. 2006
    ..Antagonizing Ets-1 might be of benefit in attenuating CCN2 expression in fibrosis, arthritis and cancer, and may be useful in modulating the outcome of these disorders...
  27. ncbi Targeting the TGFbeta, endothelin-1 and CCN2 axis to combat fibrosis in scleroderma
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology, Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada N6A 5C1
    Cell Signal 20:1409-14. 2008
    ..In particular the potent pro-fibrotic proteins endothelin-1 (ET-1) and CCN2 (connective tissue growth factor, CTGF) are believed to play an essential role in this process. This review summarizes these recent crucial observations...
  28. ncbi Signaling in fibrosis: targeting the TGF beta, endothelin-1 and CCN2 axis in scleroderma
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology, Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, Canada
    Front Biosci (Elite Ed) 1:115-22. 2009
    ..This review summarizes these recent crucial observations with emphasis on the disease scleroderma...
  29. ncbi Loss of protein kinase Cepsilon results in impaired cutaneous wound closure and myofibroblast function
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, Canada N6A 5C1
    J Cell Sci 121:3459-67. 2008
    ..These results suggest that loss of PKCepsilon severely impairs myofibroblast formation and function, and that targeting PKCepsilon may be beneficial in selectively modulating wound healing and fibrotic responses in vivo...
  30. ncbi The skinny on CCN2
    Andrew Leask
    Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 2:93-4. 2008
    ..A recent report written by Tan and colleagues (Am J Physiol Cell Physiol 295: C740-C751 2008) shows that CCN2 inhibits adipocyte differentiation. This commentary summarizes these observations...
  31. ncbi The role of endothelin-1 signaling in the fibrosis observed in systemic sclerosis
    Andrew Leask
    Department of Dentistry, Dental Sciences Building, University of Western Ontario, London, ON N6A5C1, Canada
    Pharmacol Res 63:502-3. 2011
    ..However, clinically, endothelin receptor antagonism alone has had mixed results. This minireview summarizes these observations...
  32. ncbi CCN1: a novel target for pancreatic cancer
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 5:123-4. 2011
    ..A recent exciting report by Haque and colleagues (Mol Cancer. 2011 Jan 13;10:8) provides strong evidence that CCN1 (cyr61) is a potential therapeutic target in pancreatic cancer...
  33. ncbi Possible strategies for anti-fibrotic drug intervention in scleroderma
    Andrew Leask
    Division of Oral Biology, Department of Dentistry, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 5:125-9. 2011
    ..Moreover, peroxisome proliferator-activated receptor (PPAR)γ also appears to act by intervening in TGFβ signaling. This review discusses these potential candidates for antifibrotic therapy in SSc...
  34. ncbi Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation
    Andrew Leask
    Dental Sciences Building, London ON N6A 5C1, Canada
    Circ Res 106:1675-80. 2010
    ....
  35. ncbi When there's smoke there's…scleroderma: evidence that patients with scleroderma should stop smoking
    Andrew Leask
    Department of Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 5:67-8. 2011
    ..This commentary discusses this recent publication which suggests that physicians should encourage SSc patients to stop smoking immediately...
  36. ncbi TGFbeta, cardiac fibroblasts, and the fibrotic response
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, Canada N6A 5C1
    Cardiovasc Res 74:207-12. 2007
    ....
  37. ncbi All in the CCN family: essential matricellular signaling modulators emerge from the bunker
    Andrew Leask
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology, and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada
    J Cell Sci 119:4803-10. 2006
    ....
  38. ncbi CCN2/decorin interactions: a novel approach to combating fibrosis?
    Andrew Leask
    Department of Dentistry, University of Western Ontario, London, NGA 5C1, ON, Canada
    J Cell Commun Signal 5:249-50. 2011
    ..Thus it is conceivable that this peptide could be used in the future as a novel antifibrotic approach...
  39. ncbi Towards an anti-fibrotic therapy for scleroderma: targeting myofibroblast differentiation and recruitment
    Andrew Leask
    Division of Oral Biology, Department of Dentistry, Schulich School of Medicine and Dentistry University of Western Ontario, Dental Sciences Building, London ON N6A 5C1 Canada
    Fibrogenesis Tissue Repair 3:8. 2010
    ..TGFbeta, ET-1 and CCN2 appear to contribute to myofibroblast differentiation; PDGF appears to be involved with pericyte recruitment. Thus, different therapeutic strategies may exist for targeting the multisystem fibrotic disorder SSc...
  40. ncbi Eureka! Ets a target for fibrosis!
    Andrew Leask
    Department of Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 5:325-6. 2011
    ..Am J Respir Cell Mol Biol. 2011 May 11) shows that mice containing a version of ets2 that is incapable of being phosphorylated are resistant to bleomycin-induced lung fibrosis. This latter paper is the subject of this commentary...
  41. ncbi Hijacking ZIP codes: posttanscriptional regulation of CCN2 by nucleophosmin
    Andrew Leask
    Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 3:85-6. 2009
    ....
  42. ncbi CCN2: a bona fide target for anti-fibrotic drug intervention
    Andrew Leask
    Departments of Dentistry and Physiology and Pharmacology, University of Western Ontario, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 5:131-3. 2011
    ..in Fibrogenesis Tissue Repair 4:1-4, 2011). This commentary addresses recent data indicating that CCN2 appears to represent a key central mediator of fibrosis and a good target for anti-fibrotic drug intervention...
  43. ncbi Will o' the wisp: CCN4 as a novel molecular target in osteoarthritis
    Andrew Leask
    Department of Dentistry, University of Western Ontario, London, ON, Canada, NGA 5C1
    J Cell Commun Signal 5:51-2. 2011
    ..This commentary summarizes these exciting findings...
  44. ncbi Endogenous endothelin-1 signaling contributes to type I collagen and CCN2 overexpression in fibrotic fibroblasts
    Xu Shi-Wen
    Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK
    Matrix Biol 26:625-32. 2007
    ..Thus endogenous endothelin signaling contributes to the fibrotic phenotype of fibrotic fibroblasts, suggesting that antagonizing endothelin receptors may be of benefit in combating fibrotic disease...
  45. ncbi Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts
    Xu Shi-Wen
    Royal Free Hospital, University College London, London, UK
    Arthritis Rheum 56:4189-94. 2007
    ..The goal of this study was to assess whether ET-1 is a downstream mediator of the profibrotic effects of TGFbeta in lung fibroblasts...
  46. ncbi Requirement of transforming growth factor beta-activated kinase 1 for transforming growth factor beta-induced alpha-smooth muscle actin expression and extracellular matrix contraction in fibroblasts
    Xu Shi-Wen
    University College London Royal Free Campus, London, UK
    Arthritis Rheum 60:234-41. 2009
    ..The present study was undertaken to assess whether TGFbeta-activated kinase 1 (TAK1) acts downstream of FAK/Src to mediate fibrogenic responses in fibroblasts...
  47. ncbi FAK is required for TGFbeta-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix-remodeling phenotype
    Shangxi Liu
    Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
    Mol Biol Cell 18:2169-78. 2007
    ....
  48. ncbi Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblasts
    Yunliang Chen
    University College London, London, UK
    Arthritis Rheum 58:577-85. 2008
    ....
  49. ncbi Rac1 expression by fibroblasts is required for tissue repair in vivo
    Shangxi Liu
    Department of Physiology and Pharmacology, Division of Oral Biology, Schulich School of Medicine and Dentistry, Canadian Institute of Health Research Group in Skeletal Development and Remodeling, University of Western Ontario, London, Ontario, Canada
    Am J Pathol 174:1847-56. 2009
    ..Thus, Rac1 is an essential signaling integrator that is required for normal wound healing and dermal homeostasis...
  50. ncbi Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagen
    Markella Ponticos
    Royal Free and University College Medical School, London, UK
    Arthritis Rheum 60:2142-55. 2009
    ....
  51. ncbi GSK-3beta in mouse fibroblasts controls wound healing and fibrosis through an endothelin-1-dependent mechanism
    Mohit Kapoor
    Division of Oral Biology and Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada
    J Clin Invest 118:3279-90. 2008
    ..These results suggest that targeting the GSK-3beta pathway or ET-1 may be of benefit in controlling tissue repair and fibrogenic responses in vivo...
  52. ncbi CCN2 is necessary for the function of mouse embryonic fibroblasts
    Laura Kennedy
    Division of Oral Biology and Department of Physiology and Pharmacology, CIHR Group in Skeletal Development and Remodeling, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, Canada N6A 5C1
    Exp Cell Res 313:952-64. 2007
    ....
  53. ncbi Expression of integrin beta1 by fibroblasts is required for tissue repair in vivo
    Shangxi Liu
    The Canadian Institute of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON N6A 5C1, Canada
    J Cell Sci 123:3674-82. 2010
    ..Addition of active TGFβ alleviated the phenotype of integrin-β1-deficient mice. Thus integrin β1 is essential for normal wound healing, where it acts, at least in part, through a TGFβ-dependent mechanism in vivo...
  54. ncbi Rac inhibition reverses the phenotype of fibrotic fibroblasts
    Shi wen Xu
    Centre for Rheumatology, Department of Medicine, University College London Royal Free Campus, London, United Kingdom
    PLoS ONE 4:e7438. 2009
    ..The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies...
  55. ncbi Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFalpha-induced MEK/ERK signalling
    Jason S Rockel
    Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A5C1, Canada
    Arthritis Res Ther 11:R8. 2009
    ..TNFalpha activates mitogen-activated kinase kinase (MEK)/extracellular regulated kinase (ERK) in chondrocytes; however, the overall functional relevance of MEK/ERK to TNFalpha-regulated gene expression in chondrocytes is unknown...
  56. ncbi Focal adhesion kinase/Src suppresses early chondrogenesis: central role of CCN2
    Daphne Pala
    Department of Physiology and Pharmacology and Division of Oral Biology, Canadian Institute of Health Research Group in Skeletal Development and Remodeling, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    J Biol Chem 283:9239-47. 2008
    ..Our results suggest a reduction in FAK/Src signaling is a critical feature permitting chondrogenic differentiation and that CCN2 operates downstream of this loss to promote chondrogenesis...
  57. ncbi Loss of peroxisome proliferator-activated receptor gamma in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis
    Mohit Kapoor
    University of Western Ontario, London, Ontario, Canada
    Arthritis Rheum 60:2822-9. 2009
    ..The aim of the present study was to examine the role of PPARgamma in a mouse model of skin scleroderma, in which mice bearing a fibroblast-specific deletion of PPARgamma were used...
  58. ncbi Role of Rac1 in a bleomycin-induced scleroderma model using fibroblast-specific Rac1-knockout mice
    Shangxi Liu
    University of Western Ontario, London, Ontario, Canada
    Arthritis Rheum 58:2189-95. 2008
    ..Rac1 plays a key role in adhesive signaling. The aim of the present study was to examine the role of Rac1 in bleomycin-induced scleroderma, using mice with a fibroblast-specific deletion of Rac1...
  59. ncbi Loss of beta1 integrin in mouse fibroblasts results in resistance to skin scleroderma in a mouse model
    Shangxi Liu
    University of Western Ontario, London, Ontario, Canada
    Arthritis Rheum 60:2817-21. 2009
    ..Beta-1 integrin plays a key role in adhesive signaling. The aim of the present study was to examine the role of beta1 integrin in a mouse model of skin scleroderma using mice bearing a fibroblast-specific deletion of beta1 integrin...
  60. ncbi CCN2 is necessary for adhesive responses to transforming growth factor-beta1 in embryonic fibroblasts
    Xu Shi-Wen
    Centre for Rheumatology, Department of Medicine, University College London Royal Free Campus, London NW3 2PF, United Kingdom
    J Biol Chem 281:10715-26. 2006
    ..Thus in embryonic fibroblasts, CCN2 is a necessary cofactor required for TGFbeta to activate the adhesive FAK/Akt/phosphatidylinositol 3-kinase cascade, FAK/Akt-dependent genes, and adhesion to matrix...
  61. ncbi Loss of PTEN expression by dermal fibroblasts causes skin fibrosis
    Sunil K Parapuram
    Department of Dentistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    J Invest Dermatol 131:1996-2003. 2011
    ..Overexpression of PTEN reduced the overexpression of type I collagen and CCN2 by dSSc fibroblasts. Thus, PTEN appears to be a potential in vivo master regulator of fibrogenesis; PTEN agonists may represent anti-fibrotic treatments...
  62. ncbi Fibroblast adhesion results in the induction of a matrix remodeling gene expression program
    Laura Kennedy
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London ON, Canada N6A 5C1
    Matrix Biol 27:274-81. 2008
    ..These results suggest that adhesion of fibroblasts to matrix during the initial phases of tissue remodeling and repair may actively contribute to the tissue repair program through the induction of pro-fibrotic gene expression...
  63. ncbi Matrix contraction by dermal fibroblasts requires transforming growth factor-beta/activin-linked kinase 5, heparan sulfate-containing proteoglycans, and MEK/ERK: insights into pathological scarring in chronic fibrotic disease
    Yunliang Chen
    Centre for Rheumatology, University College London, Royal Free Campus, UK
    Am J Pathol 167:1699-711. 2005
    ..We conclude that antagonizing MEK/ERK, TGFbeta1/ALK5, or syndecan 4 may alleviate scarring in chronic fibrotic disease...
  64. ncbi TGF-beta signaling and the fibrotic response
    Andrew Leask
    Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School, Rowland Hill St, London, UK NW3 2PF
    FASEB J 18:816-27. 2004
    ....
  65. ncbi Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblasts
    Xu Shi-Wen
    Centre for Rheumatology, University College London Royal Free Campus, London, UK
    Rheumatology (Oxford) 49:259-63. 2010
    ..The aim of the present study was to examine whether PPAR-gamma expression was reduced in skin scleroderma fibroblasts and whether PPAR-gamma agonists could suppress the persistent fibrotic phenotype of skin scleroderma fibroblasts...
  66. ncbi Epithelial cells promote fibroblast activation via IL-1alpha in systemic sclerosis
    Nima Aden
    Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital Campus, University College Medical School, University College London, London, UK
    J Invest Dermatol 130:2191-200. 2010
    ..These findings are important because biologic therapies could target epithelial-fibroblast interactions in the disease...
  67. ncbi Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis
    Xu Shi-Wen
    Centre for Rheumatology, Department of Medicine, Hampstead Campus, University College London, Rowland Hill Street, London NW3 2PF, UK
    Cytokine Growth Factor Rev 19:133-44. 2008
    ..Abnormal amplification of CTGF dependent signals results in a failure to terminate tissue repair, leading pathological scarring in conditions such as fibrosis and cancer...
  68. ncbi Constitutive ALK5-independent c-Jun N-terminal kinase activation contributes to endothelin-1 overexpression in pulmonary fibrosis: evidence of an autocrine endothelin loop operating through the endothelin A and B receptors
    Xu Shi-Wen
    Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom
    Mol Cell Biol 26:5518-27. 2006
    ....
  69. ncbi Cyclic AMP regulates extracellular matrix gene expression and metabolism in cultured primary rat chondrocytes
    Jason S Rockel
    Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
    Matrix Biol 28:354-64. 2009
    ..Collectively, these results suggest that agents that elevate cAMP signaling may impair chondrocyte function in conditions such as arthritis...
  70. ncbi Contribution of activin receptor-like kinase 5 (transforming growth factor beta receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblasts
    Yunliang Chen
    Royal Free and University College Medical School, London, UK
    Arthritis Rheum 54:1309-16. 2006
    ..CONCLUSION: Our data suggest that some of the key profibrotic features of lesional SSc fibroblasts are dependent upon ALK-5 activity. Thus, TGFbetaRI kinase-mediated signaling may contribute to dermal fibrosis in dcSSc...
  71. ncbi CCN2 is required for bleomycin-induced skin fibrosis in mice
    Shangxi Liu
    Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    Arthritis Rheum 63:239-46. 2011
    ..The aim of this study was to assess whether adult mice bearing a smooth muscle cell/fibroblast-specific deletion of CCN2 are resistant to bleomycin-induced skin scleroderma...
  72. ncbi Prostacyclin derivatives prevent the fibrotic response to TGF-beta by inhibiting the Ras/MEK/ERK pathway
    Richard Stratton
    Centre for Rheumatology, Royal Free Hospital and University College School of Medicine, London NW3 2PF, UK
    FASEB J 16:1949-51. 2002
    ..Specific inhibition of fibroblast Ras/MEK/ERK signaling might prevent fibrosis while leaving other physiological effects of TGFbeta unaltered...
  73. ncbi Gingival fibroblasts display reduced adhesion and spreading on extracellular matrix: a possible basis for scarless tissue repair?
    Fen Guo
    Department of Dentistry, University of Western Ontario, London, Ontario, Canada
    PLoS ONE 6:e27097. 2011
    ..Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury...
  74. ncbi Transcriptional profiling of the scleroderma fibroblast reveals a potential role for connective tissue growth factor (CTGF) in pathological fibrosis
    Andrew Leask
    Centre for Rheumatology, Royal Free and University College Medical School, University College London, London, UK
    Keio J Med 53:74-7. 2004
    ..Thus the constitutive overexpression of CTGF by fibroblasts present in fibrotic lesions would be expected to directly contribute to chronic, persistent fibrosis...
  75. ncbi Thrombospondin 1 is a key mediator of transforming growth factor β-mediated cell contractility in systemic sclerosis via a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent mechanism
    Yunliang Chen
    School of Life Sciences, University of Westminster, London, UK
    Fibrogenesis Tissue Repair 4:9. 2011
    ..In this report we investigate whether activation of latent TGFβ by TSP1 plays a key role in matrix contraction by normal and scleroderma fibroblasts...
  76. ncbi Integrin β1 is necessary for the maintenance of corneal structural integrity
    Sunil K Parapuram
    Department of Dentistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    Invest Ophthalmol Vis Sci 52:7799-806. 2011
    ..Given that integrins are essential for cell/extracellular matrix interactions, the authors tested the hypothesis that integrin expression by keratocytes is essential for corneal structure and function...
  77. ncbi Mechanical tension increases CCN2/CTGF expression and proliferation in gingival fibroblasts via a TGFβ-dependent mechanism
    Fen Guo
    Department of Dentistry, University of Western Ontario, London, Ontario, Canada
    PLoS ONE 6:e19756. 2011
    ....
  78. ncbi Scar wars: is TGFbeta the phantom menace in scleroderma?
    Andrew Leask
    Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON N6A 5C1, Canada
    Arthritis Res Ther 8:213. 2006
    ..Recently, the signaling pathways through which TGFbeta activates a fibrotic program have been elucidated and, as a consequence, several possible points for anti-fibrotic drug intervention in SSc have emerged...
  79. ncbi Insights into the molecular mechanism of chronic fibrosis: the role of connective tissue growth factor in scleroderma
    Andrew Leask
    Center for Rheumatology, Royal Free and University College Medical School, University College London, Royal Free Campus, London, UK
    J Invest Dermatol 122:1-6. 2004
    ..This review discusses recent information regarding insights into connective tissue growth factor biology and, using scleroderma as a model system, the part connective tissue growth factor might play in fibrotic disease...
  80. ncbi Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis
    Andrew Leask
    Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill St, London NW3 2PF, UK
    Curr Rheumatol Rep 4:136-42. 2002
    ....
  81. ncbi Gene expression profiling reveals novel TGFbeta targets in adult lung fibroblasts
    Elisabetta A Renzoni
    Interstitial Lung Disease Unit, Royal Brompton Hospital, Imperial College of Science, Technology and Medicine, Emmanuel Kaye Building, 1B Manresa Road, SW3 6LR, London, UK
    Respir Res 5:24. 2004
    ..Even though the effects of TGFbeta on the gene expression of several proteins have been investigated in several lung fibroblast cell lines, the global pattern of response to this cytokine in adult lung fibroblasts is still unknown...
  82. ncbi CCN2 is not required for skin development
    Shangxi Liu
    Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Bldg, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 5:179-82. 2011
    ..Thus, although recently we have shown that CCN2 is required for fibrogenesis in postnatal mice, CCN2 is not required for skin development during embryogenesis...
  83. ncbi The gene expression profile induced by Wnt 3a in NIH 3T3 fibroblasts
    Shaoqiong Chen
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, Canada, N6A 5C1
    J Cell Commun Signal 1:175-83. 2007
    ..These results suggest that Wnts induce genes promoting fibroblast differentiation towards angiogenesis and matrix remodeling, at the expense of skeletal development...
  84. ncbi Ceramide inhibits CCN2 expression in fibroblasts
    Laura Kennedy
    CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, N6A 5C1, Canada
    J Cell Commun Signal 2:19-23. 2008
    ..C2 ceramide reduced the ability of TGFbeta to induce the generic Smad responsive promoter/reporter construct SBE-luciferase. These results suggest that C2 ceramide reduces the action of TGFbeta in fibroblasts via Smad antagonism...
  85. ncbi CTGF expression in mesangial cells: involvement of SMADs, MAP kinase, and PKC
    Youjun Chen
    FibroGen, Inc, 225 Gateway Boulevard, South San Francisco, CA 94080, USA
    Kidney Int 62:1149-59. 2002
    ..The induction of excess matrix in renal fibrosis seems to be mediated, at least in part, by the transforming growth factor-beta (TGF-beta)-mediated induction of connective tissue growth factor (CTGF) in mesangial cells...
  86. ncbi Gene regulation of connective tissue growth factor: new targets for antifibrotic therapy?
    Ingrid E Blom
    Department of Pathology, H04 312, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
    Matrix Biol 21:473-82. 2002
    ..In addition, alternative therapies targeting CTGF effects are proposed which might lead to a favorable outcome of wound repair and fibrosis...
  87. ncbi Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts
    Andrew Leask
    FibroGen, Inc, South San Francisco, California 94080, USA
    J Biol Chem 278:13008-15. 2003
    ..Thus Smads, Ras/MEK/ERK, protein kinase C, and fibroblast-enriched factors that bind GAGGAATGG act together to drive the TGF-beta-mediated induction of CTGF in fibroblasts...
  88. ncbi Constitutive connective tissue growth factor expression in scleroderma fibroblasts is dependent on Sp1
    Alan Holmes
    Royal Free and University College Medical School, Center for Rheumatology, Department of Medicine, Rowland Hill St, London, United Kingdom NW3 2PF
    J Biol Chem 278:41728-33. 2003
    ..Thus, the constitutive overexpression of CTGF in SSc fibroblasts seems to be independent of TGFbeta signaling but dependent at least in part on Sp1...
  89. ncbi The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biology
    Andrew Leask
    Center for Rheumatology, Department of Medicine, Royal Free, University College London, Rowland Hill Sreet, London NW3 PF, U K
    Biochem Cell Biol 81:355-63. 2003
    ..This review summarizes the current state of knowledge regarding CTGF biology...
  90. ncbi Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model
    James M Mason
    Department of Pathology, North Shore-Long Island Jewish Research Institute and New York University School of Medicine, Manhasset, New York 11030, USA
    J Biol Chem 277:407-15. 2002
    ..These findings provide a new insight on the actions of lefty and suggest that this cytokine plays an active role in remodeling of the extracellular matrix in vivo...
  91. ncbi CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin
    Yunliang Chen
    Centre for Rheumatology, Royal Free and University College Medical School, University College London (Royal Free Campus, Hampstead, London NW3 2PF, United Kingdom
    Mol Biol Cell 15:5635-46. 2004
    ..These results are consistent with the notion that a principal function of CCN2 is to modulate receptor/ligand interactions in vivo...
  92. ncbi Endothelin-1 induces expression of matrix-associated genes in lung fibroblasts through MEK/ERK
    Shi wen Xu
    Centre for Rheumatology, Department of Medicine, Royal Free and University College London, United Kingdom
    J Biol Chem 279:23098-103. 2004
    ..Our results suggest that ET-1 induces a program of matrix synthesis in lung fibroblasts and that ET-1 may play a key role in connective tissue deposition during wound repair and in pulmonary fibrosis...
  93. ncbi The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts
    Baiqiu Wang
    Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine University Hospitals Case Medical Center, Cleveland, OH 44106, USA
    J Mol Cell Cardiol 45:193-7. 2008
    ..Consistent with this observation, KLF15 mediated repression of the CTGF promoter is rescued by P/CAF overexpression. Our result implicates KLF15 as a novel negative regulator of CTGF expression and cardiac fibrosis...
  94. ncbi Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts
    Xu Shi-Wen
    Centre for Rheumatology, Royal Free and University College Medical School, London NW3 2PF, United Kingdom
    Mol Biol Cell 15:2707-19. 2004
    ..Thus, blocking ET-1 or the PI3-kinase/Akt cascades might be beneficial in reducing scar formation in pulmonary fibrosis...
  95. ncbi Activation of key profibrotic mechanisms in transgenic fibroblasts expressing kinase-deficient type II Transforming growth factor-{beta} receptor (T{beta}RII{delta}k)
    Christopher P Denton
    Centre for Rheumatology, Royal Free and University College Medical School, Hampstead Campus, London NW3 2PF, United Kingdom
    J Biol Chem 280:16053-65. 2005
    ..Our study demonstrates that altered high affinity TGFbeta receptor function may lead to ligand-dependent activation of downstream signaling, and provides further evidence of a pivotal role for sustained TGFbeta overactivity in fibrosis...
  96. ncbi Curcumin prevents and reverses murine cardiac hypertrophy
    Hong Liang Li
    Division of Cardiology, Heart and Stroke Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto, Ontario, Canada
    J Clin Invest 118:879-93. 2008
    ..Our results indicate that curcumin has the potential to protect against cardiac hypertrophy, inflammation, and fibrosis through suppression of p300-HAT activity and downstream GATA4, NF-kappaB, and TGF-beta-Smad signaling pathways...