MiR-4756 promotes albumin-induced renal tubular epithelial cell epithelial-to-mesenchymal transition and endoplasmic reticulum stress via targeting Sestrin2

Journal of Cellular Physiology
Yijie JiaYao-Ming Xue

Abstract

Accumulating evidence indicates that proteinuria promotes the progression of diabetic kidney disease (DKD) and induces renal epithelial tubular cell epithelial-to-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress, but the mechanism remains unclear. In our previous research, we found that miR-4756 levels were increased in the urinary extracellular vesicles of type 2 diabetes mellitus patients with macroalbuminuria. In a preliminary study, we found that miR-4756 may be derived from renal tubular epithelial cells, but its role has not been elucidated. Albumin stimulation significantly increased miR-4756 levels in HK-2 cells. In addition, an miR-4756 mimic accelerated albumin-stimulated HK-2 cell EMT and ER stress, and an miR-4756 inhibitor suppressed these events. We then found that miR-4756 targeted the 3'-untranslated region (UTR) of Sestrin2 and directly suppressed Sestrin2 expression. Furthermore, the induction of EMT and ER stress by the overexpression of miR-4756 was abolished by Sestrin2 overexpression. Moreover, the overexpression of miR-4756 increased ERK1/2 activation and decreased 5' monophosphate-activated protein kinase activation. Thus, our study provides evidence that miR-4756 accelerates the proces...Continue Reading

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Citations

Aug 9, 2020·Clinical and Experimental Nephrology·Wei ZhangHao Zhang
Dec 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jie Wang BJunlian Gu
May 12, 2020·Mechanisms of Ageing and Development·Xiaolan FanMingyao Yang
Aug 28, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Nutthapoom Pathomthongtaweechai, Somchai Chutipongtanate
Apr 4, 2021·International Journal of Molecular Sciences·Przemysław A StemporPaula Dobosz
Apr 17, 2021·Frontiers in Medicine·Jingsheng ChangYifei Zhong
Aug 17, 2021·Oxidative Medicine and Cellular Longevity·Lihua NiXiaoyan Wu
Oct 6, 2021·In Vitro Cellular & Developmental Biology. Animal·Shuyue ShengYaoming Xue
Oct 6, 2021·Journal of Extracellular Vesicles·Yujia YinXipeng Wang

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