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Genomes and Genes | Andrew LeaskSummaryAffiliation: University College London Country: UK Publications
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Publications
TGF-beta signaling and the fibrotic responseAndrew 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....- Insights into the molecular mechanism of chronic fibrosis: the role of connective tissue growth factor in sclerodermaAndrew 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... - Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblastsXu 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... - Endogenous endothelin-1 signaling contributes to type I collagen and CCN2 overexpression in fibrotic fibroblastsXu 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... - Epithelial cells promote fibroblast activation via IL-1alpha in systemic sclerosisNima 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... - 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 fibroblastsXu 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... - Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagenMarkella Ponticos
Royal Free and University College Medical School, London, UK
Arthritis Rheum 60:2142-55. 2009.... - Contribution of activin receptor-like kinase 5 (transforming growth factor beta receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblastsYunliang 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... - Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblastsYunliang Chen
University College London, London, UK
Arthritis Rheum 58:577-85. 2008.... - Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblastsXu 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... - Transcriptional profiling of the scleroderma fibroblast reveals a potential role for connective tissue growth factor (CTGF) in pathological fibrosisAndrew 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... - Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosisXu 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... - Thrombospondin 1 is a key mediator of transforming growth factor ?-mediated cell contractility in systemic sclerosis via a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent mechanismYunliang Chen
School of Life Sciences, University of Westminster, London, UK
Fibrogenesis Tissue Repair 4:9. 2011..abstract:.. - 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 diseaseYunliang 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... - The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biologyAndrew 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... - Constitutive connective tissue growth factor expression in scleroderma fibroblasts is dependent on Sp1Alan 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... - Gene expression profiling reveals novel TGFbeta targets in adult lung fibroblastsElisabetta 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... - Connective tissue growth factor: a new and important player in the pathogenesis of fibrosisAndrew 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.... - Pericytes display increased CCN2 expression upon culturingXu 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... - Thrombospondin 1 in hypoxia-conditioned media blocks the growth of human microvascular endothelial cells and is increased in systemic sclerosis tissuesLuke 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:.. - The induction of CCN2 by TGFbeta1 involves Ets-1Jonathan 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... - Focal adhesion kinase/Src suppresses early chondrogenesis: central role of CCN2Daphne 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... - Fibroblast adhesion results in the induction of a matrix remodeling gene expression programLaura 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... - Targeting the TGFbeta, endothelin-1 and CCN2 axis to combat fibrosis in sclerodermaAndrew 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... - Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblastsAndrew 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... - The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblastsBaiqiu 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... - GSK-3beta in mouse fibroblasts controls wound healing and fibrosis through an endothelin-1-dependent mechanismMohit 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... - FAK is required for TGFbeta-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix-remodeling phenotypeShangxi 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.... - CTGF expression in mesangial cells: involvement of SMADs, MAP kinase, and PKCYoujun 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... - Prostacyclin derivatives prevent the fibrotic response to TGF-beta by inhibiting the Ras/MEK/ERK pathwayRichard 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... - 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... - Endothelin-1 induces expression of matrix-associated genes in lung fibroblasts through MEK/ERKShi 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... - 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 fibroblastsXu 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... - CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectinYunliang 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... - 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... - CCN2 is necessary for adhesive responses to transforming growth factor-beta1 in embryonic fibroblastsXu 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... - 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... - 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 receptorsXu 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.... - TGFbeta, cardiac fibroblasts, and the fibrotic responseAndrew 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.... - All in the CCN family: essential matricellular signaling modulators emerge from the bunkerAndrew 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.... - CCN2 is necessary for the function of mouse embryonic fibroblastsLaura 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.... - 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 modelJames 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... - Role of Rac1 in a bleomycin-induced scleroderma model using fibroblast-specific Rac1-knockout miceShangxi 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... - Curcumin prevents and reverses murine cardiac hypertrophyHong 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...