Abstract
Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ function seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.
Highlights
Fibrosis is defined as an inappropriate repair by connective tissue characterized by excessive deposition of collagen and other extracellular matrix (ECM) components, promoting disruption of tissue homeostasis
This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role in systemic sclerosis
Recent studies have established that PPARγ is a negative regulator of profibrotic signal-induced collagen synthesis and blunts fibrogenesis in a wide variety of organs
Summary
Fibrosis is defined as an inappropriate repair by connective tissue characterized by excessive deposition of collagen and other extracellular matrix (ECM) components, promoting disruption of tissue homeostasis. Nonfibroblastic cell lineages (such as epithelial or endothelial cells or adipocytes) can differentiate into fibroblasts and myofibroblasts through a process called epithelial-mesenchymal transition (EMT) [2,3,4] Regulation of these cellular transitions, collagen gene expression, and ECM accumulation is tightly controlled. Besides TGF-β, multiple cytokines, growth factors, and chemokines regulate collagen production, ECM accumulation, and mesenchymal cell function and are expressed abnormally in fibrotic diseases. These mediators, such as connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), interleukin (IL)-4, IL-6, IL-13, and IL-8, interact with TGF-β and directly contribute to the pathogenesis of fibrosis and might represent potential targets for antifibrotic therapy [11]. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role in systemic sclerosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
