the pparγ agonist rosiglitazone is antifibrotic for scleroderma lung fibroblasts mechanisms of action and differential racial effectspparγ受体激动剂罗格列酮对硬皮病antifibrotic肺成纤维细胞的作用机理和微分种族的影响.pdfVIP

Hindawi Publishing Corporation Pulmonary Medicine Volume 2012, Article ID 545172, 9 pages doi:10.1155/2012/545172 Research Article The PPARγ Agonist Rosiglitazone Is Antifibrotic for Scleroderma Lung Fibroblasts: Mechanisms of Action and Differential Racial Effects Galina S. Bogatkevich, Kristin B. Highland, Tanjina Akter, and Richard M. Silver Division of Rheumatology and Immunology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 912, Charleston, SC 29425-6370, USA Correspondence should be addressed to Galina S. Bogatkevich, bogatkev@ Received 6 May 2011; Accepted 26 August 2011 Academic Editor: Athol Wells Copyright © 2012 Galina S. Bogatkevich et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. 1. Introduct