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

Abstract：

:Renal ischemia-reperfusion injury is a leading cause of acute kidney injury; the pathogenesis of which remains poorly understood and effective therapies are 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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Hao J,Wei Q,Mei S,Li L,Su Y,Mei C,Dong Z

doi

10.1016/j.kint.2016.07.017

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

106-118

issue

1

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(16)30355-6

journal_volume

91

pub_type

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