The Effect of Cyclosporine on P-cadherin Expression in Experimental Diabetic Nephropathy and Glucose-Stimulated Podocytes

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.ope