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


CONCLUSIONS
Both HV and AII were critical for the development of GN, and HIF-1alpha remarkably attenuated the progression of GN.
Kudo
Yoshihiro
Y
Department of Laboratory Medicine, Kochi Medical School, Kochi, Japan.
Kakinuma
Yoshihiko
Y
Mori
Yasukiyo
Y
Morimoto
Norihito
N
Karashima
Takashi
T
Furihata
Mutsuo
M
Sato
Takayuki
T
Shuin
Taro
T
Sugiura
Tetsuro
T
D000804:Angiotensin II / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D002470:Cell Survival; D003435:Crotalid Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005921:Glomerulonephritis / Q000503:physiopathology* / Q000517:prevention & control*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017841:Trimeresurus
D003435:Crotalid Venoms; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000804:Angiotensin II