MicroRNA-122-5p ameliorates tubular injury in diabetic nephropathy via FIH-1/HIF-1α pathway

Diabetes kidney disease (DKD) affects approximately one-third of diabetes patients, however, the specific molecular mechanism of DKD remains unclear, and there is still a lack of effective therapies. Here, we demonstrated a significant increase of microRNA-122-5p (miR-122-5p) in renal tubular cells in STZ induced diabetic nephropathy (DN) mice. Moreover, inhibition of miR-122-5p led to increased cell death and serve tubular injury and promoted DN progression following STZ treatment in mice, whereas supplementation of miR-122-5p mimic had kidney protective effects in this model. In addition, miR-122-5p suppressed the expression of factor inhibiting hypoxia-inducible factor-1 (FIH-1) in vitro models of DN. microRNA target reporter assay further verified FIH-1 as a direct target of miR-122-5p. Generally, FIH-1 inhibits the activity of HIF-1 alpha. Our in vitro study further indicated that overexpression of HIF-1 alpha by transfection of HIF-1 alpha plasmid reduced tubular cell death, suggesting a protective role of HIF-1 alpha in DN. Collectively, these findings may unveil a novel miR-122-5p/FIH-1/HIF-1 alpha pathway which can attenuate the DN progression.

Automated summary

In this study, researchers investigated the role of miR-122-5p in diabetic nephropathy (DN) and found that increased levels of miR-122-5p promoted the progression of DN, while inhibition of miR-122-5p had negative effects and supplementation of miR-122-5p mimic had protective effects in a mouse model. The study also revealed that miR-122-5p suppressed the expression of FIH-1, which inhibits the activity of HIF-1α. Additionally, overexpression of HIF-1α reduced cell death in tubular cells, indicating a protective role in DN.