MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury

Wang, I‐Kuan; Sun, Kuo‐Ting; Tsai, Tsung-Hsun; Chen, Chia‐Wen; Chang, Shih‐Sheng; Yu, Tung‐Min; Yen, Tzung‐Hai; Lin, Feng‐Yen; Huang, Chiu‐Ching; Li, Chi Yuan

doi:10.1016/j.lfs.2015.07.002

Cited by 49 publications

(32 citation statements)

References 40 publications

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“…13–17 Notably, while some of the miRNAs mediate kidney injury during IRI, others may play protective roles. 18–20 Accordingly, investigation of these miRNAs may suggest therapeutic strategies for IRI-related kidney diseases. In this study, we specifically examined the role and regulation of miR-17-5p in renal IRI.…”

Section: Introductionmentioning

confidence: 99%

Induction of microRNA-17-5p by p53 protects against renal ischemia-reperfusion injury by targeting death receptor 6

Hao

Wei

Mei

et al. 2017

Kidney International

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Renal ischemia-reperfusion injury is a leading cause of acute kidney injury; the pathogenesis of which remains poorly understood and effective therapies still lacking. Here we tested whether microRNAs, identified as critical regulators of cell health and disease, are involved in this process. We found that miR-17-5p was significantly up-regulated during renal ischemia-reperfusion injury in mice and during hypoxia in cultured renal tubular cells. In cultured cells, MiR-17-5p directly inhibited the expression of death receptor 6 (DR6) and attenuated apoptosis during hypoxia. Blockade of miR-17-5p abolished the suppression of DR6 and facilitated caspase activation and apoptosis. In vivo, an miR-17-5p mimic suppressed DR6 expression and protected against renal ischemia-reperfusion injury. We further verified that miR-17-5p induction during renal ischemia-reperfusion injury was dependent on p53. Inhibition of p53 with pifithrin-α or a dominant-negative mutant led to the repression of miR-17-5p expression under hypoxia in vitro. Moreover, miR-17-5p induction during renal ischemia-reperfusion injury was attenuated in proximal tubule p53 knockout mice, supporting the role of p53 in miR-17-5p induction in vivo. Thus, p53/miR-17-5p/DR6 is a new protective pathway in renal ischemia-reperfusion injury and may be targeted for the prevention and treatment of ischemic acute kidney injury.

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Section: Introductionmentioning

confidence: 99%

Induction of microRNA-17-5p by p53 protects against renal ischemia-reperfusion injury by targeting death receptor 6

Hao

Wei

Mei

et al. 2017

Kidney International

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“…A recent study has indicated that miR-137 inhibits hypoxia-induced mitophagy by reducing expression of the mitophagy receptor, thereby leading to inadequate interaction between the receptor and light chain (LC) 3 (11), further indicating that miR has a role in modulating autophagy. Furthermore, it has been demonstrated that miR-20a-5p mediates hypoxia-induced autophagy by targeting the autophagy related 16-like 1 gene in ischemic kidney injury (12), and in cardiomyocytes, the inhibition of miR-497 is able to ameliorate anoxia/reoxygenation injury by suppressing cell apoptosis and enhancing autophagy (13). miR-17-5p is a member of the miR-17–92 cluster, which is located on human chromosome 13q31 (14).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-17-5p mediates hypoxia-induced autophagy and inhibits apoptosis by targeting signal transducer and activator of transcription 3 in vascular smooth muscle cells

Hao

Wang

Jiao

2017

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate hypoxia-induced apoptosis and autophagy in vascular smooth muscle cells (VSMCs) and the underlying molecular mechanisms of microRNA (miR)-17-5p responses in an anaerobic environment. The results revealed that miR-17-5p expression was significantly upregulated in VSMCs subjected to hypoxic conditions (P<0.05) and lower miR-17-5p levels were observed in ethyl 3,4-dihydroxybenzoate-treated and hypoxia inducible factor-1 loss-of-function cells. Additionally, it was demonstrated that miR-17-5p is associated with hypoxia-induced autophagy, which was confirmed by upregulating the light chain 3-II/LC3-I ratio and downregulating nucleoporin p62. Cell apoptosis was inhibited in response to hypoxia, and levels of pro-apoptotic proteins B-cell lymphoma 2-associated X protein and p-caspase were markedly decreased when VSMCs were subjected to hypoxic conditions. Furthermore, expression of signal transducer and activator of transcription 3 (STAT3) decreased when cells were transfected with overexpressing miR-17-5p and subjected to hypoxic conditions, and the combination of miR-17-5p loss-of-function and hypoxia induced greater upregulation in the protein expression of STAT3 compared with a single treatment for hypoxia in VSMCs. In conclusion, miR-17-5p may be a novel hypoxia-responsive miR and hypoxia may induce protective autophagy and anti-apoptosis in VSMCs by targeting STAT3.

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“…Autophagy is an early response to ischemia and proceeds the appearance of apoptotic cells 23,94,105,106 . In mice, suppression of autophagy leads to apoptosis during reperfusion and to worse renal outcome including more severe renal dysfunction and histologic injury ( Figure 2 ) 23,94,107 .…”

Section: Introductionmentioning

confidence: 99%

Autophagy and Tubular Cell Death in the Kidney

Havasi

Dong

2016

Seminars in Nephrology

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Summary Many common renal insults such as ischemia and toxic injury primarily target the tubular epithelial cells especially the highly metabolically active proximal tubular segment. Tubular epithelial cells are particularly dependent on autophagy to maintain homeostasis and respond to stressors. The pattern of autophagy in the kidney has a unique spatial and chronological signature. Recent evidence shows that there is a complex crosstalk between autophagy and various cell death pathways. The purpose of this review is to specifically discuss the interplay between autophagy and cell death in the renal tubular epithelia. It is imperative to review this topic because recent discoveries have improved our mechanistic understanding of the autophagic process and have highlighted its broad clinical applications, making autophagy a major target for drug development.

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MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury

Cited by 49 publications

References 40 publications

Induction of microRNA-17-5p by p53 protects against renal ischemia-reperfusion injury by targeting death receptor 6

Induction of microRNA-17-5p by p53 protects against renal ischemia-reperfusion injury by targeting death receptor 6

MicroRNA-17-5p mediates hypoxia-induced autophagy and inhibits apoptosis by targeting signal transducer and activator of transcription 3 in vascular smooth muscle cells

Autophagy and Tubular Cell Death in the Kidney

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