Please use this identifier to cite or link to this item:
https://hdl.handle.net/20.500.12530/32907
Title: | HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p. | |
Authors: | ||
Mesh: | ||
Issue Date: | 2017 | |
Citation: | Sci Rep.2017 01;(7):41099 | |
Abstract: | Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity. In addition, HIF-1α inhibition induced proximal tubule cells proliferation but it did not induce compensatory apoptosis, both in vivo. In vitro, HIF-1α knockdown in HK2 cells subjected to hypoxia/reoxygenation (H/R) promote cell entry into S phase, correlating with in vivo data. HIF-1α interference leads to downregulation of miR-127-3p and induction of its target gene Bcl6 in vivo. Moreover, modulation of miR-127-3p in HK2 cells subjected to H/R results in EMT regulation: miR127-3p inhibition promote loss of e-cadherin and induction of α-SMA and collagen I. In conclusion, HIF-1α induction during reperfusion is a protector mechanism implicated in a normal renal tissue repair after I/R. | |
PMID: | 28106131 | |
URI: | https://hdl.handle.net/20.500.12530/32907 | |
Rights: | openAccess | |
Appears in Collections: | Fundaciones e Institutos de Investigación > IIS H. U. Ramón y Cajal > Artículos | |
Files in This Item:
File | Description | Size | Format | |
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PMC5247697.pdf | 3.26 MB | Adobe PDF | View/Open |
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