MicroRNA-451 regulates p38 MAPK signaling by targeting of Ywhaz and suppresses the mesangial hypertrophy in early diabetic nephropathy

Diabetic nephropathy (DN) is a major diabetic complication. However, the initiating molecular events triggering DN are unknown. In this study we focused on microRNA-451 (miR-451), which is downregulated during early DN. We found that miR-451 negatively regulated the expression of Ywhaz through Ywhaz 3′UTR and that Ywhaz was required for the miR-451-mediated downregulation of p38 MAPK signalling. Moreover, over-expression of miR-451 inhibits glomerular mesangial cell proliferation in vitro and in vivo. These findings suggest that the growth-inhibitory effect of miR-451 may be explained in part by miR-451-induced suppression of Ywhaz and p38 MAPK signalling, providing evidence for the potential role of miR-451 in early DN.

► miR-451 negatively regulates the expression of Ywhaz through Ywhaz 3′UTR. ► Ywhaz is required for the miR-451-mediated downregulation of p38 MAPK signalling. ► Over-expression of miR-451 inhibits glomerular mesangial cell proliferation.