The Effect of Cyclosporine on P-cadherin Expression in Experimental Diabetic Nephropathy and Glucose-Stimulated Podocytes.
- Author:
Shin Wook KANG
1
;
Tae Hyun YOO
;
Hyung Jong KIM
;
Hoon Young CHOI
;
Joo Seong KIM
;
Dong Sub JUNG
;
Jin Ju KIM
;
Seung Jae KWAK
;
Seung Hyeok HAN
;
Dong Ki KIM
;
Tae Hee LEE
;
Jung Eun LEE
;
Dae Suk HAN
;
Dong Ryeol RYU
Author Information
1. Department of Internal Medicine, College of Medicine, Yonsei University, Korea.
- Publication Type:Original Article
- Keywords:
Diabetic nephropathy;
Proteinuria;
Podocyte;
Cyclosporin A;
P-cadherin
- MeSH:
Albuminuria;
Animals;
Blotting, Western;
Cadherins*;
Cyclosporine*;
Diabetic Nephropathies*;
Ethanol;
Glucose;
Mice;
Podocytes*;
Proteinuria;
Rats;
Rats, Sprague-Dawley;
RNA, Messenger;
Streptozocin;
Transforming Growth Factor beta1
- From:Korean Journal of Nephrology
2007;26(1):23-33
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: We investigated whether Cyclosporin A (CsA) had the anti-proteinuric effect in diabetic rats and whether it was associated with the alteration of P-cadherin expression. METHODS: Sprague-Dawley rats were injected with diluent (C, N=16) or streptozotocin intraperitoneally (DM, N=16). Eight rats in each group were treated with 10% ethanol or with 1.5 mg/kg/day of CsA (C+CsA and DM+CsA) for 6 weeks. Immortalized mouse podocytes were cultured in media with 5.6 mM glucose (LG), LG+CsA (10-8 M), LG+TGF-beta1, 30 mM glucose (HG), or HG+CsA. Real time-PCR and Western blot were performed for P-cadherin and TGF-beta1 mRNA and protein expression, respectively, with sieved glomeruli and cell lysates. RESULTS: Urinary albumin excretion was significantly higher in DM compared with C rats, and CsA treatment inhibited the increase in albuminuria in DM rats. Glomerular P-cadherin mRNA and protein expression in DM were decreased compared with C rats, and these decreases were significantly inhibited by CsA. Glomerular TGF-beta1 mRNA and protein expression were higher in DM than C rats, and CsA treatment inhibited the increase in TGF-beta1 expression in DM. P-cadherin mRNA and protein expression in HG and LG+TGF-beta1 podocytes were lower than LG cells, and these HG-induced decrements were restored by CsA. CONCLUSION: CsA treatment reduces urinary albumin excretion in DM rats. P-cadherin expression is decreased under diabetic conditions, which is ameliorated by CsA. In addition, inhibition of the increase in glomerular TGF-beta1 expression under diabetic conditions by CsA seems to restore the P-cadherin expression, resulting in the decrease in albuminuria.
