Upregulation of renal renin-angiotensin system in mouse diabetic nephropathy
2005
Tamura, J.(Hokkaido Univ., Sapporo (Japan)) | Konno, A. | Hashimoto, Y. | Kon, Y.
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 2. 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 beta-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 2 were newly distributed on the flattered epithelial cells in the dilated distal tubules in the cortex as well as the collecting ducts in the cortex and medulla, and were demonstrated more intensity in CBA/N mice than in CBA/J mice. Micro dissectional analysis in both models revealed a higher incidence of RAS-related gene expression in CBA/J, Ren 2 mice than in CBA-N, Ren 1 mice.
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