Mauch C, Eckes B, Hunzelmann N, Oono T, Kozlowska E, Krieg T
Department of Dermatology, University of Cologne, Germany.
J Invest Dermatol. 1993 Jan;100(1):92S-96S. doi: 10.1111/1523-1747.ep12356293.
Scleroderma is characterized by an excessive deposition of collagen in all involved organs. This is due to an overproduction of extracellular matrix (ECM) molecules following induction of gene expression, whereas there is no evidence that the composition of the connective tissue matrix is altered. Several in vivo studies and in vitro experiments suggest that a close interaction between inflammatory cells and fibroblasts is required for the initial activation of fibroblasts. TGF-beta presumably plays an important role, but other cytokines, e.g., PDGF or FGF, may also be involved. Many of the ECM molecules have been shown to interact closely with fibroblasts and provide signals that regulate fibroblast metabolism. The cellular response towards those signals is a further aspect of fibrosis that has attracted attention during recent years. The altered expression of receptor proteins on the cell surface of scleroderma fibroblasts for example might explain in part the lack of down-regulation of collagen synthesis in late phases of the disease. This review summarizes the alterations of connective tissue in scleroderma, and discusses the role of cytokines as well as the ECM for the regulation of fibroblast function and their implication for the development of fibrosis.
硬皮病的特征是在所有受累器官中胶原蛋白过度沉积。这是由于基因表达诱导后细胞外基质（ECM）分子的过度产生，而没有证据表明结缔组织基质的组成发生了改变。多项体内研究和体外实验表明，炎症细胞与成纤维细胞之间的密切相互作用是成纤维细胞初始激活所必需的。转化生长因子-β（TGF-β）可能起重要作用，但其他细胞因子，如血小板衍生生长因子（PDGF）或成纤维细胞生长因子（FGF）也可能参与其中。许多ECM分子已被证明与成纤维细胞密切相互作用，并提供调节成纤维细胞代谢的信号。细胞对这些信号的反应是近年来引起关注的纤维化的另一个方面。例如，硬皮病成纤维细胞表面受体蛋白表达的改变可能部分解释了疾病后期胶原蛋白合成缺乏下调的原因。本综述总结了硬皮病中结缔组织的改变，并讨论了细胞因子以及ECM在调节成纤维细胞功能中的作用及其对纤维化发展的影响。
