Ihn Hironobu
Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Curr Rheumatol Rep. 2005 Apr;7(2):156-62. doi: 10.1007/s11926-005-0069-9.
Excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that various cytokines such as transforming growth factor (TGF)-beta and their signaling pathways are key mediators of tissue fibrosis as a consequence of ECM accumulation in the pathogenesis of fibrosis such as SSc. TGF-beta regulates diverse biologic activities including cell growth, cell death or apoptosis, cell differentiation, and ECM synthesis. TGF-beta is known to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. This paper focuses on the possible role of ECM, various cytokines, especially TGF-beta signal transduction pathways in the pathogenesis of fibrosis in SSc.
皮肤、肺和其他器官中细胞外基质（ECM）过度沉积是系统性硬化症（SSc）的一个标志。SSc的发病机制仍知之甚少，但越来越多的证据表明，各种细胞因子，如转化生长因子（TGF）-β及其信号通路，是组织纤维化的关键介质，这是ECM在诸如SSc等纤维化发病机制中积累的结果。TGF-β调节多种生物学活性，包括细胞生长、细胞死亡或凋亡、细胞分化以及ECM合成。已知TGF-β可诱导间充质细胞中ECM蛋白的表达，并刺激蛋白酶抑制剂的产生，从而防止ECM的酶解。本文重点探讨ECM、各种细胞因子，尤其是TGF-β信号转导通路在SSc纤维化发病机制中的可能作用。
