Glomerular repair retardation via blocking of angiotensin II type 1a receptor pathway in a mouse glomerulonephritis model.

Abstract

BACKGROUND/AIMS:

To examine the role of the angiotensin II (ATII) type 1a receptor (AT1-R) pathway in renal tissue damage and repair, we investigated reversible glomerular injury in a mouse model of habu snake venom (HSV)-induced glomerulonephritis using AT1-R-deficient (AT1a-/-) mice and AT1-R antagonist-treated mice.

METHODS:

Experimental glomerulonephritis was induced by single administration of HSV to AT1a(+/+) mice (HSV group) and AT1a(-/-) mice (KO-HSV group) and AT1-R antagonist-treated BL6 mice (HSV-ARB group). Morphological change and expression levels of type IV collagen, CD31, and vascular endothelial growth factor (VEGF) were analyzed.

RESULTS:

The HSV group showed increased mesangial matrix expansion on day 7, which returned to preinjection levels by day 56, while mes-angial matrix expansion and increased type IV collagen expression were seen throughout days 7 to 56 in the KO-HSV group. The KO-HSV group showed fewer CD31-positive capillary loops and a marked decrease in the number of VEGF-positive cells in the glomeruli than the HSV group. VEGF administration to the KO-HSV group facilitated glomerular capillary repair and reconstruction. The HSV-ARB group showed the same delay in glomerular repair as that seen in the KO-HSV group.

CONCLUSION:

Our results indicate that blocking of the ATII-AT1R pathway delays glomerular repair via angiogenesis inhibition, followed by reduced induction of VEGF.

• Authors: Waka Hayashi, Yoko Obata, Tomoya Nishino, Shinichi Abe, Kumiko Io, Akira Furusu, Katsushige Abe, Masanobu Miyazaki, Takeshi Sugaya, Takehiko Koji, Shigeru Kohno
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 122 Issue 1-2 Pg. 13-22 ( 2012) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 23446008 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biphenyl Compounds
• Collagen Type IV
• Crotalid Venoms
• Receptor, Angiotensin, Type 1
• Tetrazoles
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Angiotensin II
• candesartan cilexetil

Topics

• Angiotensin II (metabolism)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Benzimidazoles (pharmacology)
• Biphenyl Compounds (pharmacology)
• Collagen Type IV (metabolism)
• Crotalid Venoms (toxicity)
• Disease Models, Animal
• Glomerulonephritis (metabolism, pathology)
• Kidney Glomerulus (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptor, Angiotensin, Type 1 (deficiency, genetics, metabolism)
• Renin-Angiotensin System (drug effects)
• Signal Transduction (drug effects)
• Tetrazoles (pharmacology)
• Trimeresurus
• Vascular Endothelial Growth Factor A (metabolism)