Silencing of miR-150-5p Ameliorates Diabetic Nephropathy by Targeting SIRT1/p53/AMPK Pathway

Frontiers in Physiology

Huiqian Zhang¹  Cheng Zhao²  Yun Luo²  Wenmin Dong³  Ying Chen³ 

[1] Shanghai Research Institute of TCM Literature, Shanghai, China;Shanghai TCM-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China;Shanghai University of Traditional Chinese Medicine, Shanghai, China;

关键词: diabetic nephropathy;    microRNAs;    SIRT1;    p53;    autophagy;   

DOI  :  10.3389/fphys.2021.624989

来源: DOAJ

【 摘 要 】

Diabetic nephropathy (DN) is a common complication of diabetes and an important cause of end-stage renal disease. Increasing evidence suggests that microRNAs (miRNAs) regulate the development of DN. In a preliminary study, high levels of miR-150-5p were detected in the serum and urine of patients with DN. Consequently, we investigated the effect and mechanism of action of miR-150-5p in DN in vitro and in vivo. Our results showed that inhibition of miR-150-5p reversed high glucose-induced podocyte injury and Streptozocin (STZ)-induced diabetic nephropathy in mice. Further analysis revealed that miR-150-5p targeted the 3′ untranslated region (UTR) of sirtuin 1 (SIRT1), consequently decreasing SIRT1 levels in podocytes. Importantly, we found that the silencing of miR-150-5p promoted the interaction between SIRT1 and p53, causing the suppression of p53 acetylation in podocytes and kidney tissue. This resulted in the stimulation of AMP-activated protein kinase (AMPK)-dependent autophagy. In conclusion, our study demonstrated that the silencing of miR-150-5p played a reno-protective role in DN mice through targeting SIRT1.

【 授权许可】

Unknown