Korean J Nephrol.  2006 Nov;25(6):903-912.

The Effect of High Glucose on Renin-Angiotensin System (RAS) in Podocytes

• Yoo TH
• Ryu DR
• Lee JJ
• Kim JJ
• Jung DS
• Kwak SJ
• Xu ZG
• Kim JS
• Kim HJ
• Choi HY
• Han DS
• Kang SW

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.

Keyword

Diabetic nephropathy; Podocytes; High glucose; Angiotensinogen; Angiotensin II

MeSH Terms

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
Angiotensin I
Angiotensin II
Angiotensinogen
Culture Media, Conditioned
Glucose
Mannitol
RNA, Messenger
Renin