Hypoxia inducible factor 1-alpha (hif-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival
Author
Conde, Elisa; Alegre, Laura; Blanco-Sánchez, Ignacio; Sáenz-Morales, David; Aguado-Fraile, Elia; Ponte, Belén; Ramos, Edurne; Sáiz, Ana; Jiménez, Carlos Víctor; Ordóñez, Ángel; López-Cabrera, Manuel; Del Peso, Luis; Ortiz de Landázuri, Manuel; Liaño, Fernando; Selgas Gutiérrez, Rafael; Sánchez-Tomero, José Antonio; García-Bermejo, María LauraEntity
UAM. Departamento de Bioquímica; UAM. Departamento de MedicinaPublisher
Public Library of ScienceDate
2012-03-14Citation
10.1371/journal.pone.0033258
Plos One 7.3 (2012): e33258
ISSN
1932-6203 (online)DOI
10.1371/journal.pone.0033258Funded by
This work was supported by grants from Fondo de Investigación Sanitaria FIS PI06/539, FIS PS09/02183, from Fundación Médica de Investigación Mutua Madrileña, FMMA 185/2006 and from Comunidad de Madrid CAM S-SAL 0311/2006 to MLGB; MOL and LPProject
Comunidad de Madrid. S2006/SAL-0311Subjects
Cell Survival; Hypoxia-Inducible Factor 1; Immunohistochemistry; Kidney Transplantation; TOR Serine-Threonine Kinases; MedicinaRights
© 2012 Conde et al.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
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Google Scholar:Conde, Elisa
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Alegre, Laura
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Blanco-Sánchez, Ignacio
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Sáenz-Morales, David
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Aguado-Fraile, Elia
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Ponte, Belén
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Ramos, Edurne
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Sáiz, Ana
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Jiménez, Carlos Víctor
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Ordóñez, Ángel
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López-Cabrera, Manuel
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Del Peso, Luis
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Ortiz de Landázuri, Manuel
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Liaño, Fernando
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Selgas Gutiérrez, Rafael
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Sánchez-Tomero, José Antonio
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García-Bermejo, María Laura
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