P-Cadherin is Decreased in Glucose-Stimulated Podocytes and in Experimental Diabetic Nephropathy / 대한신장학회잡지
Korean Journal of Nephrology
; : 494-503, 2003.
Article
em Ko
| WPRIM
| ID: wpr-51863
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WPRO
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.
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WPRIM
Assunto principal:
Proteinúria
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RNA Mensageiro
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Diafragma
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Imuno-Histoquímica
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Caderinas
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Western Blotting
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Ratos Sprague-Dawley
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Estreptozocina
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Nefropatias Diabéticas
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Podócitos
Limite:
Animals
Idioma:
Ko
Revista:
Korean Journal of Nephrology
Ano de publicação:
2003
Tipo de documento:
Article