The Effect of High Glucose on Renin-Angiotensin System (RAS) in Podocytes.
- Author:
Tae Hyun YOO
1
;
Dong Ryeol RYU
;
Jin Ji LEE
;
Jin Ju KIM
;
Dong Sub JUNG
;
Seung Jae KWAK
;
Zhong Gao XU
;
Joo Sung KIM
;
Hyung Jong KIM
;
Hoon Young CHOI
;
Dae Suk HAN
;
Shin Wook KANG
Author Information
1. Department of Internal Medicine, NHIMC Ilsan Hospital, Korea.
- Publication Type:Original Article
- Keywords:
Diabetic nephropathy;
Podocytes;
High glucose;
Angiotensinogen;
Angiotensin II
- MeSH:
Angiotensin I;
Angiotensin II;
Angiotensinogen;
Animals;
Blotting, Western;
Culture Media, Conditioned;
Diabetic Nephropathies;
Glucose*;
Mannitol;
Mesangial Cells;
Mice;
Podocytes*;
Renin;
Renin-Angiotensin System*;
RNA, Messenger
- From:Korean Journal of Nephrology
2006;25(6):903-912
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
The renin-angiotensin system (RAS) plays an important role in the pathogenesis of diabetic nephropathy. Recently, the activation of local RAS in mesangial cells by high glucose has been reported. However, little is known about the changes of RAS in podocytes under diabetic conditions. In this study, we examined whether RAS activation was induced in high glucose- stimulated podocytes. Immortalized mouse podocytes were exposed to medium containing 5.6 mM glucose (NG), NG+24.4 mM mannitol, or 30 mM glucose(HG). mRNA and protein expression of RAS components were determined by real time-PCR and Western blot, respectively. Angiotensin I (AI) and angiotensin II (AII) concentrations, angiotensin-converting enzyme (ACE) levels, and renin activity were also determined. Angiotensinogen (AGT) mRNA expression was significantly increased in HG-stimulated podocytes. In addition, AI and AII concentrations were significantly higher in HG-treated cell lysates and in their conditioned media. However, there were no differences in renin activity and ACE levels among the groups. AII type 1 receptor (AT1R) mRNA and protein expression were also increased by 288% (p<0.01) and 170% (p< 0.05) in HG-stimulated podocytes compared to NG- treated cells. In conclusion, HG induced AGT mRNA expression, resulting in increases in AI and AII levels. These findings suggest that increased AII production along with increased AT1R expression in podocytes under diabetic conditions may well be considered as factors actively involved in the pathogenesis of diabetic nephropathy.
