P-Cadherin is Decreased in Glucose-Stimulated Podocytes and in Experimental Diabetic Nephropathy.
- Author:
Dong Ryeol RYU
1
;
Zhong Gao XU
;
Tae Hyun YOO
;
Jae Hyun CHANG
;
Dong Sub JUNG
;
Su Hyun LEE
;
Jin Ju KIM
;
Kyu Hun CHOI
;
Ho Yung LEE
;
Dae Suk HAN
;
Shin Wook KANG
Author Information
1. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea. kswkidney@yumc.yonsei.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
P-cadherin;
High glucose;
Podocyte;
Diabetic nephropathy;
Proteinuria
- MeSH:
Animals;
Blotting, Western;
Cadherins*;
Diabetic Nephropathies*;
Diaphragm;
Glomerular Filtration Barrier;
Glucose;
Immunohistochemistry;
Mannitol;
Mice;
Podocytes*;
Proteinuria;
Rats;
Rats, Sprague-Dawley;
RNA, Messenger;
Streptozocin
- From:Korean Journal of Nephrology
2003;22(5):494-503
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Proteinuria is a cardinal feature of glomerular disease including diabetic nephropathy, and glomerular filtration barrier is considered as a filter restricting protein excretion in urine. We tested whether the expression of P-cadherin, a molecule known to be located at the slit diaphragm, was altered by high glucose in cultured podocytes in vitro and by diabetes in vivo. METHODS: In vitro, immortalized mouse podocytes were cultured in media with 5.6 mM glucose (NG), NG+24.4 mM mannitol (NG+M), or 30 mM glucose (HG) for 7 days at 37dgrees C. Cell lysates were used for RT-PCR and Western blot. For animal studies, twelve Sprague-Dawley rats were injected with diluent (Control, C, N=6) or streptozotocin (DM, N=6) intraperitoneally, and were sacrificed after 6 weeks. RT-PCR and Western blot for P-cadherin mRNA and protein expression, respectively, were performed with sieved glomeruli, and immunohistochemistry with renal tissue. RESULTS: HG significantly reduced P-cadherin mRNA and protein expression in cultured podocytes by 47% and 62%, respectively (p<0.05). Twenty-four hour urinary albumin excretion was significantly higher in DM (12.80+/-1.12 mg/day) compared to C rats (3.15+/-0.24 mg/day) (p<0.05). Glomerular P-cadherin mRNA expression was significantly lower in DM than that in C rats (p<0.05). P-cadherin protein expression assessed by Western blot and immunohistochemistry showed a similar pattern. CONCLUSION: Exposure of podocytes to HG in vitro and diabetes in vivo reduced P-cadherin mRNA and protein expression. These findings suggest that the decrease in P-cadherin expression is connected to the early changes of diabetic nephropathy and thus may contribute to the development of proteinuria.
