Ihn Hironobu
Department of Dermatology & Plastic and Reconstructive Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
J Dermatol Sci. 2008 Feb;49(2):103-13. doi: 10.1016/j.jdermsci.2007.05.014. Epub 2007 Jul 12.
Excessive extracellular matrix deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). Fibroblasts isolated from sclerotic lesions in patients with SSc and cultured in vitro are characterized by increased synthesis of collagen and other extracellular matrix components, consistent with the disease phenotype. Thus, cultured scleroderma fibroblasts serve as a principal experimental model for studying the mechanisms involved in extracellular matrix overproduction in SSc. The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that transforming growth factor-beta (TGF-beta) is a key mediator of tissue fibrosis as a consequence of extracellular matrix accumulation in the pathology of SSc. TGF-beta regulates diverse biological activities including cell growth, cell death or apoptosis, cell differentiation, and extracellular matrix synthesis. TGF-beta is known to induce the expression of extracellular matrix proteins in mesenchymal cells and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the extracellular matrix. This review focuses on the possible role of autocrine TGF-beta signaling in the pathogenesis of SSc.
皮肤、肺和其他器官中细胞外基质过度沉积是系统性硬化症（SSc）的一个标志。从SSc患者硬化病变中分离并在体外培养的成纤维细胞，其特征是胶原蛋白和其他细胞外基质成分的合成增加，这与疾病表型一致。因此，培养的硬皮病成纤维细胞是研究SSc中细胞外基质过度产生所涉及机制的主要实验模型。SSc的发病机制仍知之甚少，但越来越多的证据表明，转化生长因子-β（TGF-β）作为SSc病理学中细胞外基质积累的结果，是组织纤维化的关键介质。TGF-β调节多种生物学活性，包括细胞生长、细胞死亡或凋亡、细胞分化以及细胞外基质合成。已知TGF-β可诱导间充质细胞中细胞外基质蛋白的表达，并刺激蛋白酶抑制剂的产生，从而防止细胞外基质的酶解。本综述重点关注自分泌TGF-β信号在SSc发病机制中的可能作用。
