Hypoxia-inducible factor-1alpha is involved in the attenuation of experimentally induced rat glomerulonephritis

Nephron Exp Nephrol. 2005;100(2):e95-103. doi: 10.1159/000084575. Epub 2005 Mar 17.

Abstract

Background/aim: Among various kidney disease models, there are few rat glomerulonephritis (GN) models that develop in a short time, and with mainly glomerular lesions. Hypoxia-inducible factor (HIF)-1alpha is a transcriptional factor that induces genes supporting cell survival, but the involvement of HIF-1alpha in attenuating the progression of GN remains to be elucidated. We developed a new model of rat GN by coadministration of angiotensin II (AII) with Habu snake venom (HV) and investigated whether HIF-1alpha is involved in renal protection.

Methods: Male Wistar rats were unilaterally nephrectomized on day 1, and divided into 4 groups on day 0; N group (no treatment), HV group, A group (AII), and H+A group (HV and AII). To preinduce HIF-1alpha, cobalt chloride (CoCl2) was injected twice before injections of HV and AII in 11 rats.

Results: GN was detected only in the H+A group; observed first on day 2 and aggravated thereafter. HIF-1alpha was expressed in the glomeruli and renal tubules in the A and H+A groups. In the H+A group, GN was remarkably reduced by CoCl2 pretreatment (44.9 to 12.2%, p < 0.01).

Conclusion: Both HV and AII were critical for the development of GN, and HIF-1alpha remarkably attenuated the progression of GN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / administration & dosage
  • Angiotensin II / physiology*
  • Animals
  • Cell Survival
  • Crotalid Venoms / administration & dosage
  • Crotalid Venoms / pharmacology*
  • Disease Models, Animal
  • Disease Progression
  • Glomerulonephritis / physiopathology*
  • Glomerulonephritis / prevention & control*
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology*
  • Male
  • Rats
  • Rats, Wistar
  • Trimeresurus

Substances

  • Crotalid Venoms
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Angiotensin II