Getting Out of a Sticky Situation: Targeting the Myofibroblast in Scleroderma



Andrew Leask*
Departments of Dentistry and Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, N6A 5C1, Canada


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© Andrew Leask; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) 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 Departments of Dentistry and Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, N6A 5C1, Canada; Tel: 1-519-661-2111, Ext. 81102; E-mail: Andrew.Leask@schulich.uwo.ca


Abstract

There is no treatment for the fibrosis observed in scleroderma (systemic sclerosis, SSc). Although genome-wide expression profiling has suggested that differences in gene expression patters between non-lesional and lesional skin are minimal, phenotypically these areas of tissue are quite different. In fact, lesional areas of scleroderma patients can be distinguished by the presence of a differentiated form of fibroblast, termed the myofibroblast. This cell type expresses the highly contractile protein α-smooth muscle actin (α-SMA). Fibroblasts isolated from SSc lesions excessively synthesize, adhere to and contract extracellular matrix (ECM) and display activated adhesive signaling pathways. Strategies aimed at blocking myofibroblast differentiation, persistence and activity are therefore likely to be useful in alleviating the fibrosis in scleroderma.

Keywords: PDGF, TGFβ, endothelin, rac, PPARγ, Smad1, pericyte, egr-1, CCN2, CTGF, PKCε..