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KMID : 0359920070260010023
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Korean Journal of Nephrology
2007 Volume.26 No. 1 p.23 ~ p.33
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The Effect of Cyclosporine on P-cadherin Expression in Experimental Diabetic Nephropathy and Glucose-Stimulated Podocytes
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Kang Shin-Wook
Lee Tae-Hee
Yoo Tae-Hyun
Lee Jung-Eun
Jung Dong-Sub
Kim Jin-Ju
Kwak Seung-Jae
Han Dae-Suk
Kim Hyung-Jong
Han Seung-Hyeok
Kim Dong-Kie
Choi Hoon-Young
Kim Joo-Seong
Ryu Dong-Ryeol
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Abstract
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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-β1, 30 mM glucose (HG), or HG＋CsA. Real time-PCR and Western blot were performed for P-cadherin and TGF-β1 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-β1 mRNA and protein expression were higher in DM than C rats, and CsA treatment inhibited the increase in TGF-β1 expression in DM. P-cadherin mRNA and protein expression in HG and LG＋TGF-β1 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-β1 expression under diabetic conditions by CsA seems to restore the P-cadherin expression, resulting in the decrease in albuminuria.
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KEYWORD
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Diabetic nephropathy, Proteinuria, Podocyte, Cyclosporin A, P-cadherin
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