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Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival

Conde, Elisa
Alegre, Laura
Blanco-Sánchez, Ignacio
Sáenz-Morales, David
Aguado-Fraile, Elia
Ramos, Edurne
Sáiz, Ana
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Published in PLOS ONE. 2012, vol. 7, no. 3, p. e33258
Abstract Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.
Keywords AdultAgedAnimalsCell Hypoxia/drug effectsCell Survival/drug effectsEpithelial Cells/enzymology/pathologyFemaleGene Expression Regulation/drug effectsHumansHypoxia-Inducible Factor 1, alpha Subunit/metabolismImmunohistochemistryKidney TransplantationKidney Tubular Necrosis, Acute/complications/pathologyKidney Tubules, Proximal/drug effects/metabolism/pathologyMaleMiddle AgedOxygen/pharmacologyProto-Oncogene Proteins c-akt/metabolismRatsReperfusion Injury/complications/genetics/metabolism/pathologySignal Transduction/drug effectsTOR Serine-Threonine Kinases/metabolismTranscription, Genetic/drug effectsTransplantation, HomologousYoung Adult
PMID: 22432008
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Research group Néphrologie - Ramon y Cajal (Madrid)
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CONDE, Elisa et al. Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival. In: PLOS ONE, 2012, vol. 7, n° 3, p. e33258. doi: 10.1371/journal.pone.0033258 https://archive-ouverte.unige.ch/unige:90188

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Deposited on : 2016-12-08

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