Signaling in fibrosis: targeting the TGF beta, endothelin-1 and CCN2 axis in scleroderma.
Fibrosis affects organs such as the skin, liver, kidney and lung and is a cause of significant morbidity. There is no therapy for fibrosis. Recent significant molecular insights into the signaling underlying fibrosis have been made. Transforming growth factor beta (TGF beta) signaling is a major contributor to fibrogenesis. The signaling mechanisms through which TGF beta induces fibrogenic responses have been under intense scrutiny. Moreover, 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 as downstream regulators or co-factors of TGF beta signaling. This review summarizes these recent crucial observations with emphasis on the disease scleroderma.
Leask
Andrew
A
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. Andrew.Leask@schulich.uwo.ca
D000818:Animals; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism*; D006801:Humans; D051381:Rats; D012595:Scleroderma, Systemic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C526317:CCN2 protein, human; D019332:Endothelin-1; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor