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Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury via the HIF-1?/miR-21 Axis.


ABSTRACT: Intestinal ischemia/reperfusion (I/R) can lead to tissue damage associated with inflammation and mucosal apoptosis. Ischemic postconditioning (IPostC), a series of repeated, brief, intermittent periods of ischemia and reperfusion, has beneficial effects against I/R-induced injury in the heart and intestine, although the underlying mechanisms for these effects remain unclear. We evaluated the involvement of microRNA-21 (miR-21) in the protective effects of IPostC in a rat model of I/R induced by superior mesenteric artery occlusion and reopening. IPostC decreased I/R injury and suppressed apoptosis in the intestinal tissues concomitant with the induction of hypoxia inducible factor 1 alpha (HIF-1?) and the upregulation of miR-21. In vitro experiments in the intestinal epithelial cell line IEC-6 showed that hypoxia induced miR-21 and this effect was abolished by silencing HIF1-?, confirming the induction of miR-21 by HIF1-?, HIF1-? or miR-21 inhibition exacerbated I/R induced apoptosis, and programmed cell death 4 (PDCD4) and Fas-L was involved in miR-21 mediated anti-apoptotic effects on intestinal epithelial cells. Knockdown of miR-21 or inhibition of HIF1-? abolished the IPostC-mediated attenuation of intestinal injury and apoptosis and the downregulation of PDCD4 and Fas-L. A potential mechanism underlying the protective effect of IPostC may therefore involve the induction of miR-21 by HIF1-? and the attenuation of apoptosis via the downregulation of PDCD4 and Fas-L.

SUBMITTER: Jia Z 

PROVIDER: S-EPMC5700993 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury via the HIF-1α/miR-21 Axis.

Jia Zhongzhi Z   Lian Weishuai W   Shi Haifeng H   Cao Chuanwu C   Han Shilong S   Wang Kai K   Li Maoquan M   Zhang Xiaoping X  

Scientific reports 20171123 1


Intestinal ischemia/reperfusion (I/R) can lead to tissue damage associated with inflammation and mucosal apoptosis. Ischemic postconditioning (IPostC), a series of repeated, brief, intermittent periods of ischemia and reperfusion, has beneficial effects against I/R-induced injury in the heart and intestine, although the underlying mechanisms for these effects remain unclear. We evaluated the involvement of microRNA-21 (miR-21) in the protective effects of IPostC in a rat model of I/R induced by  ...[more]

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