title: HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p.
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.
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Conde
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Giménez-Moyano
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Martín-Gómez
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Rodríguez
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: M Edurne
authors.initials: ME
authors.lastname: Ramos
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Elia
authors.initials: E
authors.lastname: Aguado-Fraile
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco-Sanchez
authors.affiliation: Pathology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Biomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: María Laura
authors.initials: ML
authors.lastname: García-Bermejo
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005355:Fibrosis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000150:complications / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009393:Nephritis / Q000150:complications / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators