Department of Dermatology & Plastic Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
J Dermatol. 2010 Jan;37(1):11-25. doi: 10.1111/j.1346-8138.2009.00738.x.
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)-beta/Smad signaling is likely to play a key role in the pathogenesis of SSc, and the autocrine TGF-beta 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.
系统性硬皮病（SSc）或硬皮病是一种获得性疾病，通常会导致皮肤和内脏器官纤维化。皮肤纤维化是这种疾病的标志，定义为真皮中细胞外基质（主要是 I 型胶原蛋白）的过度沉积和积累。从 SSc 患者皮损皮肤中分离出并在体外培养的成纤维细胞表现出胶原蛋白合成增加和胶原酶活性降低，与疾病表型一致。本综述重点介绍了 SSc 皮肤纤维化分子机制研究的最新进展。SSc 成纤维细胞中在转录水平上调的胶原产生涉及多种调节剂，包括细胞因子或转录因子。其中，转化生长因子（TGF）-β/Smad 信号通路可能在 SSc 的发病机制中发挥关键作用，自分泌 TGF-β信号假说可以解释 SSc 成纤维细胞中胶原启动子的内在激活。基质金属蛋白酶与金属蛋白酶组织抑制剂之间的失衡也可能导致真皮中胶原蛋白的过度积累。
