title: The PPARγ Agonist Rosiglitazone Is Antifibrotic for Scleroderma Lung Fibroblasts: Mechanisms of Action and Differential Racial Effects.
abstract: We present novel data demonstrating that the expression of PPARγ is reduced in lung fibroblasts from black SSc-ILD patients as compared to white patients. Activating PPARγ with the agonist rosiglitazone increased the expression of MMP-1 and inhibited collagen type I in lung fibroblasts isolated from white, but not black, SSc-ILD patients. Blocking the c-Met receptor abolishes rosiglitazone's effects on collagen and MMP-1 in lung fibroblasts isolated from white SSc-ILD patients, while augmenting the expression of the c-Met receptor in fibroblasts from black SSc-ILD patients replicates the effects of rosiglitazone seen in whites. We conclude that PPARγ agonists warrant consideration as potential antifibrotic drugs in patients with SSc-ILD. Differential therapeutic effects might be anticipated especially relative to racial differences and the functional expression of the c-Met receptor.
authors.affiliation: Division of Rheumatology and Immunology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 912, Charleston, SC 29425-6370, USA.
authors.forename: Galina S
authors.initials: GS
authors.lastname: Bogatkevich
authors.forename: Kristin B
authors.initials: KB
authors.lastname: Highland
authors.forename: Tanjina
authors.initials: T
authors.lastname: Akter
authors.forename: Richard M
authors.initials: RM
authors.lastname: Silver