About this Journal Submit a Manuscript Table of Contents
Pulmonary Medicine
Volume 2012 (2012), Article ID 545172, 9 pages
http://dx.doi.org/10.1155/2012/545172
Research Article

The PPARγ Agonist Rosiglitazone Is Antifibrotic for Scleroderma Lung Fibroblasts: Mechanisms of Action and Differential Racial Effects

Division of Rheumatology and Immunology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 912, Charleston, SC 29425-6370, USA

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.

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.