心肌纤维化是糖尿病心肌病（DCM）导致心力衰竭的主要发病机制。TGF-β信号是多种因素诱导心肌纤维化的共同通路。Endoglin是介导TGF-β信号转导的辅助Ⅲ型受体，选择性高表达于心肌成纤维细胞，抑制它的作用可显著限制心肌纤维化，改善心衰病人预后。我们在DCM小鼠心脏中发现显著上调的circRNA_88704来源于编码endoglin的亲本基因ENG，生物信息学分析显示它与包含ENG结合域的miR-138-5p高度匹配。据此，我们推测“circRNA_88704通过海绵吸附miR-138-5p而上调ENG表达，促进糖尿病心肌纤维化的形成”。本课题拟从细胞到整体，采用RIP、FISH、双荧光素酶等技术，揭示circRNA_88704、miR-138-5p、ENG之间的相互作用。该课题将为心脏中靶向endoglin选择性抑制TGF-β信号通路提供新思路，为诊断和防治DCM提供新的生物标记物。

Cardiac fibrosis is the critical pathogenesis for heart failure in diabetic cardiomyopathy. TGF-β signal is the common pathway in mediating fibrogenesis induced by multiple factors. Endoglin is an auxiliary type Ⅲ receptor participating in TGF-β signal transduction. It is highly expressed in cardiac fibroblasts, but not in cardiomyocytes. Reduced endoglin activity limits cardiac fibrosis and improves survival in heart failure. In the pilot study, we have found that circRNA_88704 was up-regulated in the heart of DCM mice by Arraystar circRNA chip assay. We further demonstrated that circRNA_88704 was derived from the ENG gene that encodes endoglin. Bioinformatics analysis showed that circRNA_88704 was highly matched with miRNA-138-5p in ENG 3’-UTR domain. We speculated that circRNA_88704 may up-regulate the expression of ENG through sponge adsorption of miRNA-138-5p and thus promote the formation of cardiac fibrosis in diabetes. This study will provide new target and a new biomarker for selective inhibition of TGF-β signaling pathway to prevent, diagnose and treat DCM.