Mechanisms of skin fibrosis in systemic sclerosis
Article first published online: 24 JAN 2010
© 2010 Japanese Dermatological Association
The Journal of Dermatology
Special Issue: Systemic Sclerosis (pages 1-84)
Volume 37, Issue 1, pages 11–25, January 2010
How to Cite
JINNIN, M. (2010), Mechanisms of skin fibrosis in systemic sclerosis. The Journal of Dermatology, 37: 11–25. doi: 10.1111/j.1346-8138.2009.00738.x
- Issue published online: 24 JAN 2010
- Article first published online: 24 JAN 2010
- Received 4 September 2009; accepted 15 September 2009.
- extracellular matrix;
- transcription factors
Systemic sclerosis (SSc) or scleroderma is an acquired disorder which typically results in fibrosis of the skin and internal organs. Skin fibrosis, the hallmark of this disease, is defined as excess deposition and accumulation of extracellular matrix, mainly type I collagen, in the dermis. Dermal fibroblasts isolated from lesional skin of SSc patients and cultured in vitro exhibit increased synthesis of collagen and decreased collagenase activity, consistent with the disease phenotype. This review focuses on the recent progress in the research for molecular mechanisms of skin fibrosis in SSc. The upregulated collagen production at transcriptional level in SSc fibroblasts involves various regulators including cytokines or transcription factors. Among them, transforming growth factor (TGF)-β/Smad signaling is likely to play a key role in the pathogenesis of SSc, and the autocrine TGF-β signaling hypothesis can explain intrinsic activation of collagen promoter in SSc fibroblasts. Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases might also contribute to the excess accumulation of collagen in the dermis.