International Journal of Biological Sciences

Impact factor
3.873

ISSN 1449-2288

News feeds of IJBS published articles
My Manuscript
My Account

Journal of Biomedicinenew

Theranostics

International Journal of Medical Sciences

Journal of Cancer

Oncomedicine

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Nanotheranostics

PubMed Central Indexed in Journal Impact Factor

Int J Biol Sci 2014; 10(5):530-542. doi:10.7150/ijbs.8450

Research Paper

Detailed Localization of Augmented Angiotensinogen mRNA and Protein in Proximal Tubule Segments of Diabetic Kidneys in Rats and Humans

Masumi Kamiyama1,2, Michelle K. Garner1,2, Kristina M. Farragut1,2, Tadashi Sofue4, Taiga Hara4, Takashi Morikawa6, Yoshio Konishi6, Masahito Imanishi6, Akira Nishiyama5, Hiroyuki Kobori1,2,3,5 ✉

1. Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA;
2. Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA;
3. Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA;
4. Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University School of Medicine, Kagawa 761-0793, Japan;
5. Department of Pharmacology, Kagawa University School of Medicine, Kagawa 761-0793, Japan;
6. Department of Nephrology and Hypertension, Osaka City General Hospital, Osaka 534-0021, Japan.

Abstract

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.

Keywords: angiotensin II receptor blocker, angiotensinogen, diabetic nephropathy, proximal tubule, renin-angiotensin system.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Kamiyama M, Garner MK, Farragut KM, Sofue T, Hara T, Morikawa T, Konishi Y, Imanishi M, Nishiyama A, Kobori H. Detailed Localization of Augmented Angiotensinogen mRNA and Protein in Proximal Tubule Segments of Diabetic Kidneys in Rats and Humans. Int J Biol Sci 2014; 10(5):530-542. doi:10.7150/ijbs.8450. Available from http://www.ijbs.com/v10p0530.htm