巨噬细胞-肌成纤维细胞转分化（MMT）是粥样硬化性肾动脉狭窄（ARAS）肾间质纤维化的重要环节，然而其具体调节机制尚未阐明。最新研究表明，衰老细胞源性干扰素诱导的跨膜蛋白-3（IFITM3）是导致邻近细胞衰老的关键分子，衰老细胞能高表达整合素β3（ITGB3），而ITGB3可能参与了MMT通路的激活。我们预实验证实衰老细胞能诱导ARAS模型鼠肾组织MMT的形成，同时衰老细胞来源的外泌体中高表达IFITM3。因此我们提出假设：衰老细胞来源的IFITM3能诱导巨噬细胞高表达ITGB3继而促进MMT，加速ARAS肾间质纤维化。本研究拟在前期工作基础上，通过体内外实验，运用新型的动物模型INK ATTAC小鼠及衰老细胞清除剂AP20187，利用分子生物学、荧光共聚焦显微镜、siRNA 干扰等技术，首次探讨衰老细胞诱导MMT的分子机制及其细胞内信号转导途径，为ARAS肾间质纤维化防治提供新思路。

Macrophages – myofibroblasts transition (MMT) is an important phenomenon in progression of renal interstitial fibrosis in atherosclerotic renal artery stenosis (ARAS). However, the exact mechanism has not been completely elucidated. Recent studies show that senescence cells derived interferon-induced transmembrane protein 3 (IFITM3) is a key regulator causing nearby cells senescence. In the senescence cells, integrin β3 (ITGB3) is significantly up-regulated and may have been involved in activating the pathway of MMT. Our previous studies confirmed that senescence cells could induce MMT in kidney of ARAS rats. In addition, we found that the expression of IFITM3 increased in exosomes derived from senescence cells. Therefore, we hypothesize that IFITM3 from senescence cells may induce up-regulation of ITGB3 in macrophages, which results in MMT, accelerating renal interstitial fibrosis in ARAS. Based on previous studies, we will explore the effect of senescence cell on MMT and clarify its intracellular signaling pathways in vitro and in vivo by the ways of molecular techniques, siRNA interference and fluorescence confocal microscope. The current study uses a novel animal model (INK ATTAC) and senolytic drug (AP20187). The result of this study is expected to provide novel mechanisms regarding the therapeutic targets of ARAS.