急性肾损伤(AKI)向慢性肾脏疾病(CKD)进展的机制仍未完全阐明。上皮与间质交流(EMC)在AKI向CKD进展中发挥重要作用，外泌体(exosome)是细胞交流的主要载体，能够运载microRNA到受体细胞发挥效应。本项目组前期研究发现缺血再灌注损伤肾脏microRNA-155表达显著升高；而且缺氧损伤的肾小管上皮细胞分泌exosome促进成纤维细胞增殖，抑制exosome中microRNA-155表达后成纤维细胞增殖减少，smad7表达上调。由此，本项目提出exosome运载microRNA-155介导EMC靶向smad7促进缺血再灌注后AKI向CKD进展的假说。为验证假说，本项目拟建立缺血再灌注肾损伤模型和肾小管上皮细胞缺氧模型，阐明exosome运载microRNA-155介导EMC在缺血再灌注肾损伤向CKD进展中的作用及机制，为缺血再灌注后AKI向CKD进展提供防治靶点。

The mechanisms of acute kidney injury (AKI) progression to chronic kidney disease (CKD) is not fully elucidated. Epithelial–mesenchymal communication (EMC) plays an important role in acute kidney injury (AKI) progression to chronic kidney disease (CKD). A fundamental function of exosome is to mediate intercellular communication by transferring microRNAs to recipient cells as nanovectors. Our previous studies found that the expression of microRNA-155 was up-regulated in renal acute ischemia-reperfusion injury； hypoxia stimulated exosome secretion of renal tubular epithelial cells, which can activate fibroblast proliferation; in addition, inhibition of microRNA-155 expression in exosome retarded fibroblasts proliferation and up-regulated the expression of smad7. Therefore, we hypothesize AKI progression to CKD is promoted by EMC possibly mediated by exosome-delivered microRNA-155. To validate this hypothesis, we will use model of renal acute ischemia-reperfusion injury in mice and hypoxia injury in epithelial cells，to elucidate the role and mechanism of epithelia-mesenchymal communication mediated by exosomes-delivered microRNA-155 on AKI progression to CKD, thus providing targets for prevention and treatment.