Andrew Leask

Summary

Affiliation: University of Western Ontario
Country: Canada

Publications

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Collaborators

Detail Information

Publications66

  1. 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...
  2. 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...
  3. 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...
  4. 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...
  5. 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 TGF? alleviated the phenotype of integrin-?1-deficient mice. Thus integrin ?1 is essential for normal wound healing, where it acts, at least in part, through a TGF?-dependent mechanism in vivo...
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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
    ....
  13. 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...
  14. 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...
  15. 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...
  16. 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
    ....
  17. ncbi Integrin ?1 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...
  18. ncbi Mechanical tension increases CCN2/CTGF expression and proliferation in gingival fibroblasts via a TGF?-dependent mechanism
    Fen Guo
    Department of Dentistry, University of Western Ontario, London, Ontario, Canada
    PLoS ONE 6:e19756. 2011
    ....
  19. 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...
  20. 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
    ....
  21. 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
    ....
  22. 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...
  23. 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...
  24. 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...
  25. 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...
  26. 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)? also appears to act by intervening in TGF? signaling. This review discusses these potential candidates for antifibrotic therapy in SSc...
  27. 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...
  28. 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...
  29. 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...
  30. 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
    ....
  31. 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
    ....
  32. 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...
  33. 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...
  34. 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...
  35. 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...
  36. 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...
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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...
  45. 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
    ....
  46. 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...
  47. 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...
  48. 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...
  49. 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...
  50. 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...
  51. 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...
  52. 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
    ....
  53. 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...
  54. 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...
  55. 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...
  56. 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...
  57. 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...
  58. 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
    ....
  59. 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...
  60. 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...
  61. 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...
  62. 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
    ....
  63. 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...
  64. 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...
  65. 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...
  66. 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...