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通过靶向SIRT1/p53/AMPK途径沉默miR-150-5p可改善糖尿病肾病

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

作者信息

Dong Wenmin, Zhang Huiqian, Zhao Cheng, Luo Yun, Chen Ying

机构信息

Shanghai TCM-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Front Physiol. 2021 Apr 9;12:624989. doi: 10.3389/fphys.2021.624989. eCollection 2021.

Abstract

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 and . 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.

摘要

糖尿病肾病(DN)是糖尿病常见的并发症,也是终末期肾病的重要病因。越来越多的证据表明,微小RNA(miRNA)参与调控DN的发展。在一项初步研究中,DN患者血清和尿液中检测到高水平的miR-150-5p。因此,我们研究了miR-150-5p在DN中的作用及作用机制。我们的结果表明,抑制miR-150-5p可逆转高糖诱导的小鼠足细胞损伤及链脲佐菌素(STZ)诱导的糖尿病肾病。进一步分析显示,miR-150-5p靶向沉默调节蛋白1(SIRT1)的3'非翻译区(UTR),从而降低足细胞中SIRT1的水平。重要的是,我们发现沉默miR-150-5p可促进SIRT1与p53之间的相互作用,导致足细胞和肾组织中p53乙酰化受到抑制。这导致激活AMP依赖的蛋白激酶(AMPK)自噬。总之,我们的研究表明,沉默miR-150-5p通过靶向SIRT1在DN小鼠中发挥肾脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50bf/8064124/8bc4294b640b/fphys-12-624989-g0001.jpg

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