Key result
In diabetic rats and humans, angiotensinogen protein expression was significantly increased in proximal tubule segment 1 compared to controls, suggesting its contribution to the progression of diabetic nephropathy.
Why the study?
Does olmesartan reduce augmented angiotensinogen expression in proximal tubule segments of diabetic kidneys?
Observational (n=31)
No
Does olmesartan reduce augmented angiotensinogen expression in proximal tubule segments of diabetic kidneys?
Answers are grounded in this paper and cite their sources.
Augmented proximal tubule angiotensinogen in diabetes is hypothesis-generating; leaves open whether olmesartan attenuates this in humans.
In the intrarenal renin-angiotensin system, angiotensinogen levels are well known to be increased in diabetes, and these enhanced intrarenal angiotensinogen levels may initiate the development and accelerate the progression of diabetic nephropathy. However, the specific localization of the augmented angiotensinogen in proximal tubule segments in diabetes is still unknown. We investigated the detailed localization of angiotensinogen in 3 proximal tubule segments in the diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and the control Long-Evans Tokushima Otsuka (LETO) rats. We also prepared OLETF rats treated with angiotensin II type 1 receptor blocker, olmesartan or with a combination of vasodilator agents. Moreover, biopsied samples of human kidney cortex were used to confirm the results of animal studies. We examined the co-localization of angiotensinogen with segment-specific markers by double staining using fluorescence in situ hybridization and/or immunofluorescence. Angiotensinogen mRNA expression was barely detectable in segment 1. In segment 3, the area of angiotensinogen mRNA expression was augmented in the OLETF rats compared with the LETO rats. Angiotensinogen protein expression areas in segments 1 and 3 were also increased in the OLETF rats compared with the LETO rats. Chronic treatment with olmesartan ameliorated these areas of augmented angiotensinogen expression. Biopsied human kidney samples showed similar results. These data suggest that the augmented angiotensinogen mRNA levels in segment 3 and angiotensinogen protein levels in segments 1 and 3 may contribute to the progression of diabetic nephropathy.
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Kamiyama et al. (2014) conducted an observational in Diabetic Nephropathy (n=31). In diabetic rats and humans, angiotensinogen protein expression was significantly increased in proximal tubule segment 1 compared to controls, suggesting its contribution to the progression of diabetic nephropathy.
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