MiR-191 secreted by platelet-derived microvesicles induced apoptosis of renal tubular epithelial cells and participated in renal ischemia-reperfusion injury via inhibiting CBS

Abstract

ABSTRACT In this study, we aimed to reveal the role of miR-191 in apoptosis of renal tubular epithelial cells and in the involvement of renal ischemia-reperfusion injury. Renal transplantation rat model was established. miR-191 and Cystathionine-β-synthase (CBS) were measured by qRT-PCR and Western blot. The regulation of miR-191 on CBS was detected by luciferase reporter assay. We found miR-191 expression in platelets and platelet microvesicles (P-MVs) of patients and model rats was significantly upregulated than that of health and normal rats. Also, mRNA and protein levels of CBS in renal tissues of patients were significantly downregulated than that of health and normal rats. We also found that P-MVs could transfer miR-191 to HK-2 cells. Luciferase reporter assay showed that CBS was a direct target of miR-191. In addition, we proved that P-MVs-secreted miR-191 inhibited CBS expression in HK-2 cells, and P-MVs-secreted miR-191 promoted HK-2 cell apoptosis via CBS. Finally, we verified the trends of CBS expressions, HK-2 cell apoptosis and apoptosis-related proteins in vivo were similar as the trends in vitro. Therefore, CBS was a direct target of miR-191, and miR-191 could transfer to HK-2 cells via P-MVs to decrease the expression of CBS, thus to promote cell apoptosis and renal IR injury.