四跨膜蛋白Tetraspanin 1结合Collagen I在特发性肺纤维化发病中的分子机制研究

特发性肺纤维化（IPF）发病机制未完全阐明，缺乏可行治疗手段。我们前期报道了四跨膜蛋白家族成员TSPAN1在IPF患者和小鼠肺纤维化肺组织中表达异常，参与肺泡上皮细胞凋亡和间质化过程。近期我们的结果显示：TSPAN1缺失的小鼠肺组织中细胞外基质（ECM）蛋白Collagen I、IV和整合素α6、β1、β3等表达增加，而外源性TSPAN1能显著缓解小鼠肺纤维化严重程度，Collagen I分泌减少，免疫共沉淀证实TSPAN1与Collagen I存在直接相互作用。因此，我们假设“TSPAN1作为跨膜受体直接结合Collagen I传导ECM与细胞间的信号（整合素可能是协作蛋白），参与调控IPF进程”。为证实这个设想，拟通过IPF患者样本、TSPAN1多种基因敲除小鼠和原代细胞等从临床、动物和细胞等水平系统性阐明TSPAN1在IPF中的生物学功能和作用，为IPF的诊断和治疗提供理论依据。

The pathogenesis of idiopathic pulmonary fibrosis (IPF) was not clear and there is no efficient therapy for IPF. Previously, we reported that a member of transmembrane 4 Superfamily, TSPAN1, was aberrant expressed in lung tissue of patients with IPF and pulmonary fibrosis mouse model, is involved in the process of apoptosis and interstitialization of alveolar epithelial cells. Recently, we observed that deletion of TSPAN1 promoted the expression of collagen I/IV and integrin α6/β1/β3 in lung tissue of mouse. Exogenous overexpression of TSPAN1 relieved significantly the degree of pulmonary fibrosis in mouse, decreased the expression of collagen I in lung tissue. Moreover, interaction between TSPAN1 and collagen I was confirmed by co-immunoprecipitation. Therefore, we hypothesized that" TSPAN1 act as a transmembrane receptor of collagen I and regulate the process of IPF by binding to collagen I (and cooperating with integrin)". Clarification of the hypothesis, by utilizing samples from patients with IPF, multiple TSPAN1 CKO mouse and primary cells from mouse in clinical data, mouse model and cells level, prove the biological role of TSPAN1 in IPF and further supply theoretical basis for diagnosis and target therapy of IPF.