Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in Systemic Sclerosis.

Abstract

Systemic Sclerosis (SSc) is a systemic autoimmune disease of unknown etiology with a highly complex pathogenesis that despite extensive investigation is not completely understood. The clinical and pathologic manifestations of the disease result from three distinct processes: 1) Severe and frequently progressive tissue fibrosis causing exaggerated and deleterious accumulation of interstitial collagens and other extracellular matrix molecules in the skin and various internal organs; 2) extensive fibroproliferative vascular lesions affecting small arteries and arterioles causing tissue ischemic alterations; and 3) cellular and humoral immunity abnormalities with the production of numerous autoantibodies, some with very high specificity for SSc. The fibrotic process in SSc is one of the main causes of disability and high mortality of the disease. Owing to its essentially universal presence and the severity of its clinical effects, the mechanisms involved in the development and progression of tissue fibrosis have been extensively investigated, however, despite intensive investigation, the precise molecular mechanisms have not been fully elucidated. Several recent studies have suggested that cellular transdifferentiation resulting in the phenotypic conversion of various cell types into activated myofibroblasts may be one important mechanism. Here, we review the potential role that cellular transdifferentiation may play in the development of severe and often progressive tissue fibrosis in SSc.