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

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.