Upregulation of renal renin-angiotensin system in mouse diabetic nephropathy

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The aim of this study was to clarify the role of the renal renin-angiotensin system (RAS) in diabetic nephropathy (DN) , which was induced by injection of streptozotocin (STZ). Male CBA/N and CBA/J mice were compared in this study. The former possesses a single renin gene, Ren1. whereas the latter carries two renin genes, Ren1 and Ren2. To examine the molecular dynamics of renal RAS, including renin, angiotensinogen (Agt). angiotensin-converting enzyme (Ace). angiotensin type 1 (Agtr1) and type 2 (Agtr2) receptors in experimental DN, we performed laser-microdissection (LMD) followed by reverse transcriptase nested polymerase chain reaction using each specific primer pairs and immunohistochemistry for renin and angiotensin II.CBA/N mice had a higher response after injection of STZ than CBA/J mice, showing a significant increase of the kidney/body weight ratio, although there was no significant difference between the two strains for the blood glucose level or pancreatic β-cell response. The onset of renal pathological changes associated with DN was earlier and more severe in CBA/N mice than in CBA/J mice. Distinct immunoreactivities for renin and angiotensin.These findings suggest that intrarenal RAS plays an important role in the onset of renal pathological changes associated with DN. Additionally, Ren 1 mice have more severe histopathological nephropathy than Ren1 Ren2 mice, followed by marked production of angiotensin II.
2005-08-31