Exendin-4 ameliorates high glucose-induced fibrosis by inhibiting the secretion of miR-192 from injured renal tubular epithelial cells

作者：Yijie Jia, Zongji Zheng, Meiping Guan, Qian Zhang, Li Yang, Ling Wang, Yaoming Xue · 发表于：Experimental & Molecular Medicine · 年份：2018 · DOI：10.1038/s12276-018-0084-3 · 被引用次数：54 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

Extracellular vesicles (EVs), which contain microRNA (miRNA), constitute a novel means of cell communication that may contribute to the inevitable expansion of renal fibrosis during diabetic kidney disease (DKD). Exendin-4 is effective for treating DKD through its action on GLP1R. However, the effect of exendin-4 on EV miRNA expression and renal cell communication during the development of DKD remains unknown. In this study, we found that EVs derived from HK-2 cells pre-treated with exendin-4 and high glucose (Ex-HG), which were taken up by normal HK-2 cells, resulted in decreased levels of FN and Col-I compared with EVs from HK-2 cells pre-treated with HG alone. Furthermore, we found that pretreatment with HG and exendin-4 may have contributed to a decrease in miR-192 in both HK-2 cells and EVs in a p53-dependent manner. Finally, we demonstrated that the amelioration of renal fibrosis by exendin-4 occurred through a miR-192-GLP1R pathway, indicating a new pathway by which exendin-4 regulates GLP1R. The results of this study suggest that exendin-4 inhibits the transfer of EV miR-192 from HG-induced renal tubular epithelial cells to normal cells, thus inhibiting GLP1R downregulation and protecting renal cells. This study reports a new mechanism by which exendin-4 exerts a protective effect against DKD. An existing drug for diabetic kidney disease (DKD) helps limit the spread of the condition by preventing damaged cells from communicating with healthy cells. A key characteristi...