Regulation of Matrix Remodeling by Peroxisome Proliferator-Activated Receptor-γ: A Novel Link Between Metabolism and Fibrogenesis

Jun Wei 1, Swati Bhattacharyya 1, Manu Jain 2, John Varga*, 1
1 Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, USA
2 Respiratory and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA

Article Metrics

CrossRef Citations:
Total Statistics:

Full-Text HTML Views: 5465
Abstract HTML Views: 2424
PDF Downloads: 903
Total Views/Downloads: 8798
Unique Statistics:

Full-Text HTML Views: 2290
Abstract HTML Views: 1335
PDF Downloads: 572
Total Views/Downloads: 4202

Creative Commons License
© Wei et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Division of Rheumatology, Northwestern University Feinberg School of Medicine, McGaw Pavilion M230D, 240 E Huron St, Chicago, IL 60611, USA; Tel: (312) 503-0368; Fax: (312) 503-0994; E-mail:


The intractable process of fibrosis underlies the pathogenesis of systemic sclerosis (SSc) and other diseases, and in aggregate contributes to 45% of deaths worldwide. Because currently there is no effective anti-fibrotic therapy, a better understanding of the pathways and cellular differentiation programs underlying fibrosis are needed. Emerging evidence points to a fundamental role of the nuclear hormone receptor peroxisome proliferator activated receptor-γ (PPAR-γ) in modulating fibrogenesis. While PPAR-γ has long been known to be important in lipid metabolism and in glucose homeostasis, its role in regulating mesenchymal cell biology and its association with pathological fibrosis had not been appreciated until recently. This article highlights recent studies revealing a consistent association of fibrosis with aberrant PPAR-γ expression and activity in various forms of human fibrosis and in rodent models, and reviews studies linking genetic manipulation of the PPAR-γ pathway in rodents and fibrosis. We survey the broad range of anti-fibrotic activities associated with PPAR-γ and the underlying mechanisms. We also summarize the emerging data linking PPAR-γ dysfunction and pulmonary arterial hypertension (PAH), which together with fibrosis is responsible for the mortality in patients in SSc. Finally, we consider current and potential future strategies for targeting PPAR-γ activity or expression as a therapy for controlling fibrosis.

Keywords: PPAR-γ, SPPARM, systemic sclerosis, TGF-β..