Modification in the von Hippel-Lindau protein is involved in the progression of experimentally induced rat glomerulonephritis.
OBJECTIVE
We previously demonstrated that angiotensin II (AII) combined with Habu snake venom (HV) induces glomerulonephritis (GN) in rats, with lesions being restricted to the glomeruli 2 days after the administration of both reagents, but the mechanisms inducing GN are unclear. We also indicated a role for hypoxia-inducible factor (HIF)-1alpha in attenuating the progression of GN. However, a role of the von Hippel-Lindau (VHL) protein in GN and mechanisms by which HV regulates the pathogenesis of GN remains unclear.


RESULTS
Immunohistochemical analysis revealed that VHL is weakly expressed in the renal tubules alone; however, HV caused elevated VHL expression in the injured glomeruli including endothelial cells and partially podocytes. Western blot analysis revealed that VHL expression was increased in HV-treated kidney compared with AII-treated or normal kidney. An in vitro study also showed HV-induced elevation in VHL expression. To investigate whether VHL pre-induction causes GN aggravation, we utilized thrombin, an inducer of VHL. Thrombin alone did not cause renal injuries; however, thrombin pre-treatment accelerated the development of GN even 1 day after treatment.


CONCLUSIONS
We suggest that VHL pre-induction by thrombin aggravates GN, and that the increase in VHL expression due to HV might be involved in accelerating onset of GN.
Kudo
Yoshihiro
Y
Department of Clinical Laboratory Medicine, Kochi Medical School, Kochi, Japan.
Kakinuma
Yoshihiko
Y
Iguchi
Mitsuko
M
Sato
Takayuki
T
Sugiura
Tetsuro
T
Furihata
Mutsuo
M
Shuin
Taro
T
D000804:Angiotensin II; D000818:Animals; D002460:Cell Line; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012910:Snake Venoms; D013917:Thrombin / Q000502:physiology; D017841:Trimeresurus; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
D012910:Snake Venoms; D000804:Angiotensin II; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D013917:Thrombin