The role of collagen in systemic sclerosis

Systemic Sclerosis (SSc) is a connective tissue disease that affects various organs including the skin, lungs, kidneys, and heart. The etiology is poorly understood; however, a causative agent may initiate the disease in a patient with a genetic predisposition for SSc. There are three features responsible for the clinical and pathologic manifestations of the disease: vascular lesions of small arteries, excessive deposition of collagen in skin and internal organs, and alterations of humoral and cellular immunity. Type I collagen, the major component of extracellular matrix in skin and other tissues, is a heterotrimer of two α1 and one α2 collagen polypeptides. The synthesis of both of the chain types is highly regulated by several cis-acting regulatory elements and trans-acting protein factors, which are involved in basal gene expression. Also, several cytokines have been identified that positively and negatively influence dermal fibroblast proliferation and collagen synthesis, including: TGF-β, CTGF and IFN-γ. TGF-β and CTGF are profibrotic cytokines, whereas IFN-γ is antifibrotic cytokine. Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases might also contribute to the excess accumulation of collagen in the dermis. Because of high mortality and morbidity in SSc which directly related to the extent of the fibrotic, a precise understanding of the molecular mechanism of fibrosis will help to find effective therapeutic agents for this incurable disease in the future. This review focuses on collagen genes and proteins and then factors involved in synthesis and degradation of collagen in connection with systemic sclerosis will be explained briefly.