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Open Access Open Badges Short review

Towards an anti-fibrotic therapy for scleroderma: targeting myofibroblast differentiation and recruitment

Andrew Leask

Author Affiliations

Division of Oral Biology, Department of Dentistry, Schulich School of Medicine and Dentistry University of Western Ontario, Dental Sciences Building, London ON N6A 5C1 Canada

Fibrogenesis & Tissue Repair 2010, 3:8  doi:10.1186/1755-1536-3-8

Published: 27 May 2010



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 α-smooth muscle actin (α-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 β (TGFβ), 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.


TGFβ, ET-1, CCN2 and PDGF are likely to cooperate in driving tissue repair and fibrogenic responses in fibroblasts. TGFβ, 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.