系统性硬化症纤维化机制相关信号通路的研究进展

Progress in signaling pathways related to the fibrosis mechanism in systemic sclerosis

系统性硬化症(systemic sclerosis,SSc)是一种复杂的慢性免疫系统疾病,可导致全身多处组织和器官纤维化。SSc纤维化的原因可能是成纤维细胞(fibroblast,FB)活化为肌成纤维细胞(muscle-forming fibroblasts,MFB),从而产生Ⅰ、Ⅲ型胶原、弹性蛋白、纤维连接蛋白等其他细胞外基质(extracellular matrix,ECM),而这些ECM可以严重损害皮肤、肺、心、肾等器官。目前多项研究表明TGF-β、mTOR、JAK/STAT、Wnt/β-Catenin、Hedgehog、Notch等信号通路参与了FB的增殖并向MFB的转化,从而引起ECM的大量生成和沉积。因此,本文综述了这些信号通路与SSc纤维化之间的联系,深入研究这些通路可为SSc提供有效的治疗方案。

Systemic sclerosis(SSc)is a complex and chronic autoimmune disease causing fibrosis in multiple tissues and organs.The cause of fibrosis may be related to the production of extracellular matrix(ECM)such as typeⅠandⅢcollagens,elastin and fibronectin resulting from the transformation of activated fibroblasts(FB)into muscle-forming fibroblasts(MFB).ECM could seriously damage the skin,lung,heart,kidney and other organs.At present,many studies have shown that several signaling pathways including TGF-β,mTOR,JAK/STAT,Wnt/β-Catenin,Hedgehog and Notch are involved in the proliferation of FB and the transformation of FB to MFB,which led to the production and deposition of a great quantity of ECM.Therefore,this article reviewed the relationship between these signaling pathways and fibrosis in SSc,hoping to provided reference for the development of effective treatments for SSc.