Modification in the von Hippel-Lindau protein is involved in the progression of experimentally induced rat glomerulonephritis.

Abstract

BACKGROUND/AIMS:

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.

METHODS AND 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.

CONCLUSION:

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.

• Authors: Yoshihiro Kudo, Yoshihiko Kakinuma, Mitsuko Iguchi, Takayuki Sato, Tetsuro Sugiura, Mutsuo Furihata, Taro Shuin
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 106 Issue 3 Pg. e97-106 ( 2007) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 17519558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 S. Karger AG, Basel.

Chemical References

• Snake Venoms
• Angiotensin II
• Von Hippel-Lindau Tumor Suppressor Protein
• Thrombin

Topics

• Angiotensin II
• Animals
• Cell Line
• Disease Progression
• Gene Expression Regulation (drug effects)
• Glomerulonephritis (chemically induced, metabolism, pathology)
• Humans
• Kidney Glomerulus (metabolism, pathology)
• Kidney Tubules (metabolism, pathology)
• Male
• Podocytes (metabolism, pathology)
• Rats
• Rats, Wistar
• Snake Venoms
• Thrombin (physiology)
• Trimeresurus
• Von Hippel-Lindau Tumor Suppressor Protein (genetics, metabolism)