title: Possible strategies for anti-fibrotic drug intervention in scleroderma.
abstract: There are no approved drugs for treating the fibrosis in scleroderma (systemic sclerosis, SSc). Myfibroblasts within connective tissue express the highly contractile protein α-smooth muscle actin (α-SMA) and are responsible for the excessive synthesis and remodeling of extracellular matrix (ECM) characterizing SSc. Drugs targeting myofibroblast differentiation, recruitment and activity are currently under consideration as anti-fibrotic treatments in SSc but thus far have principally focused on the transforming growth factor β (TGFβ), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) pathways, which display substantial signaling crosstalk. 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.
authors.affiliation: 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, Andrew.Leask@schulich.uwo.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask