Dentistry Publications

Title

Towards an Anti-fibrotic Therapy for Scleroderma: Targeting Myofibroblast Differentiation and Recruitment

Document Type

Article

Publication Date

5-27-2010

Journal

Fibrogenesis & Tissue Repair

Volume

3

Issue

8

URL with Digital Object Identifier

http://dx.doi.org/10.1186/1755-1536-3-8

Abstract

BACKGROUND: In response to normal tissue injury, fibroblasts migrate into the wound where they synthesize and remodel new extracellular matrix. The fibroblast responsible for this process is called the myofibroblast, which expresses the highly contractile protein alpha-smooth muscle actin (alpha-SMA). In normal tissue repair, the myofibroblast disappears. Conversely, abnormal myofibroblast persistence is a key feature of fibrotic dieases, including scleroderma (systemic sclerosis, SSc). Myofibroblasts can be derived from differentiation of local resident fibroblasts or by recruitment of microvascular pericytes.

CLINICAL PROBLEM ADDRESSED: Controlling myofibroblast differentiation and persistence is crucial for developing anti-fibrotic therapies targeting SSc.

BASIC SCIENCE ADVANCES: Insights have been recently generated into how the proteins transforming growth factor beta (TGFbeta), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) contribute to myofibroblast differentiation and pericyte recruitment in general and to the persistent myofibroblast phenotype of lesional SSc fibroblast, specifically.

RELEVANCE TO CLINICAL CARE: This minireview summarizes recent findings pertinent to the origin of myofibroblasts in SSc and how this knowledge might be used to control the fibrosis in this disease.

CONCLUSIONS: TGFbeta, ET-1, CCN2 and PDGF are likely to cooperate in driving tissue repair and fibrogenic responses in fibroblasts. TGFbeta, ET-1 and CCN2 appear to contribute to myofibroblast differentiation; PDGF appears to be involved with pericyte recruitment. Thus, different therapeutic strategies may exist for targeting the multisystem fibrotic disorder SSc.