HSP47在TAO眶周组织纤维化中的作用和机制

眶成纤维细胞是甲状腺相关眼病（TAO）病变中的效应细胞，其活化导致TAO眼眶组织增生，最终因细胞外基质特别是胶原组织的堆积导致组织纤维化。成纤维细胞是合成、分泌胶原和HSP47的主要细胞。而HSP47是胶原特异性分子伴侣，其过表达是组织器官纤维化的危险因素。我们的前期研究显示TAO眼外肌HSP47mRAN和蛋白表达明显高于对照的颞肌。推测HSP47可能参与TAO眶周组织纤维化。因此拟进一步研究：（1）TAO眶周组织纤维化与HSP47表达的关系；(2）TAO病变中高眶压对眶成纤维细胞HSP47表达及细胞功能的影响;(3）HSP47基因过表达对眶成纤维细胞功能及合成、分泌细胞外基质的影响;(4）沉默HSP47基因对眶成纤维细胞合成、分泌细胞外基质的影响，以期明确HSP47在TAO发展中对眶周组织纤维化的作用和机制，最终为防治TAO眶周组织纤维化提供新的防治靶点和策略提供理论依据。

Orbital fibroblasts as an effector is important participant in thyroid-associated ophthalmopathy (TAO), which activated could induce the proliferation, remodeling of orbital tissues, eventually fibrosis because of the accumulation of extracellular matrix, especially collagen. Orbital fibroblasts are the main cell which synthesize and secrete the collagen, as well as HSP47. We know that HSP47 is a collagen-specific molecular chaperone that assists in the correct folding and stabilization of triple-helical procollagen molecules. High expression of HSP47 results in accumulation of collagen synthesis and induces fibrosis of some tissues or organs. Our previous study showed that the expression of HSP47 mRNA of extraocular muscles of TAO than that of teporails. It is probable that HSP47 contributes to the orbital tissue fibrosis in TAO, but so far the direct evidence still unavailable. Therefore the present study is designed to investigate:1）the correlation between HSP47 level and orbital fibrosis of TAO. 2）the cell functions and morphology of orbital fibroblasts which are cultured under high pressure which is mimic the high orbital pressure of TAO. 3) the effects of overexpression of HSP47 gene on cell function and synthesis and secretion of extracellular matrix in orbital fibroblasts. 4) the intervention effect of the silent HSP47 gene expression on cell function and synthesis and secretion of extracellular matrix in orbital fibroblasts. The purpose is to clarify the effect and mechanism of HSP47 on the orbital tissues remodeling and fibrosis in TAO, and to provide theoretical basis for the following study and development of therapeutic method for orbital tissues fibrosis in TAO aiming to HSP47.