Title:Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in
Systemic Sclerosis
Volume: 20
Issue: 4
Author(s): Sergio A. Jimenez*Sonsoles Piera-Velazquez
Affiliation:
- Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and Scleroderma Center,
Thomas Jefferson University, Philadelphia 19107, USA
Keywords:
Systemic sclerosis, scleroderma, myofibroblasts, cellular transdifferentiation, growth factors, cytokines.
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.
