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Scientific article
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English

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

Published inPloS one, vol. 7, no. 3, e33258
Publication date2012
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
  • Adult
  • Aged
  • Animals
  • Cell Hypoxia/drug effects
  • Cell Survival/drug effects
  • Epithelial Cells/enzymology/pathology
  • Female
  • Gene Expression Regulation/drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
  • Immunohistochemistry
  • Kidney Transplantation
  • Kidney Tubular Necrosis, Acute/complications/pathology
  • Kidney Tubules, Proximal/drug effects/metabolism/pathology
  • Male
  • Middle Aged
  • Oxygen/pharmacology
  • Proto-Oncogene Proteins c-akt/metabolism
  • Rats
  • Reperfusion Injury/complications/genetics/metabolism/pathology
  • Signal Transduction/drug effects
  • TOR Serine-Threonine Kinases/metabolism
  • Transcription, Genetic/drug effects
  • Transplantation, Homologous
  • Young Adult
Citation (ISO format)
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
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Article (Published version)
Identifiers
ISSN of the journal1932-6203
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