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Título: | HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p |
Autor: | Conde, Elisa; Giménez-Moyano, Sara; Martín-Gómez, Laura; Rodríguez, Macarena; Ramos, M. Edurne; Aguado-Fraile, Elia; Blanco-Sánchez, Ignacio; Sáiz, Ana; García-Bermejo, María Laura | Palabras clave: | Acute kidney injury Mechanisms of disease |
Fecha de publicación: | 2017 | Editor: | Springer Nature | Citación: | Scientific Reports 7: 41099 (2017) | Resumen: | 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. | Descripción: | © The Author(s) 2017. | Versión del editor: | http://dx.doi.org/10.1038/srep41099 | URI: | http://hdl.handle.net/10261/200396 | DOI: | 10.1038/srep41099 | E-ISSN: | 2045-2322 |
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