title: Cellular responses to hypoxia after renal segmental infarction.
abstract: BACKGROUND
  Hypoxia is believed to play an important role in the pathogenesis of acute and chronic kidney disease. However, the impact of low oxygen tensions on cellular functions in the kidney and potential adaptive responses are poorly understood.
  
  
  METHODS
  In order to assess the effects of regional hypoxia, we induced large segmental renal infarcts in rats by renal artery branch ligation to create an oxygen gradient vertical to the corticomedullary axis and studied the effects on cell morphology, the induction of hypoxia-inducible transcription factors (HIF), the expression of HIF target genes, and cell proliferation.
  
  
  RESULTS
  Pimonidazol protein adduct immunohistochemistry, a marker for severe tissue hypoxia, verified a continuous area of hypoxic renal tissue extending from the cortex to the papilla, in which tubular necrosis developed subsequently. Within this area local sparing of pimonidazol staining and tissue preservation was found around arcuate veins, indicating regional oxygen supply via diffusion from venous blood. HIF-1alpha was up-regulated within 1 hour and for up to 7 days predominantly in the border zone of the infarct in tubular cells, glomerular cells, resident interstitial cells, capillary endothelial cells, and infiltrating macrophages. HIF-2alpha expression was less prominent and confined to resident and infiltrating peritubular cells in the cortex. HIF expression was colocalized with regional up-regulation of the hypoxia-inducible genes heme oxygenase-1 and vascular endothelial growth factor (VEGF), and was followed by capillary and tubular proliferation.
  
  
  CONCLUSIONS
  Our findings illustrate a marked potential of renal tissue to respond to regional ischemia and initiate adaptive reactions, including angiogenesis.
authors.affiliation: Department of Nephrology and Medical Intensive Care, Charité, Humboldt University, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenberger
authors.forename: Wanja
authors.initials: W
authors.lastname: Griethe
authors.forename: Gertrud
authors.initials: G
authors.lastname: Gruber
authors.forename: Michael
authors.initials: M
authors.lastname: Wiesener
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frei
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007238:Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D009593:Nitroimidazoles / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009593:Nitroimidazoles; D015534:Trans-Activators; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C033815:pimonidazole