| Original Article : The Effect of Cyclosporine on P-cadherin Expression in Experimental Diabetic Nephropathy and Glucose-Stimulated Podocytes |
| Shin-Wook Kang, M.D.1, Tae-Hyun Yoo, M.D.2 , Hyung-Jong Kim, M.D.3, Hoon-Young Choi, M.D.1, Joo-Seong Kim, M.D.1 , Dong-Sub Jung, M.D.1, Jin-Ju Kim, M.D.1,Seung-Jae Kwak, M.D.1, Seung Hyeok Han, M.D.1, Dong Ki Kim, M.D.1, Tae Hee Lee, M.D.1, Jung Eun Lee |
Department of Internal Medicine1
College of Medicine, Yonsei University Department of Internal Medicine2
NHIC Ilsan Hospital Department of Internal Medicine3
Pocheon Jungmun Medical College Department of Internal Medicine4
College of Medicine, Ewha Womans University, Seoul, Korea |
| 기초연구 : 당뇨 백서 사구체 및 고포도당으로 자극한 족세포에서 싸이클로스포린이 P-cadherin의 발현에 미치는 영향 |
| 강신욱1 |
| 연세대학교 의과대학 내과학교실1, 국민보험공단 일산병원 내과2, 포천중문의과대학 내과학교실3, 이화여자대학교 의과대학 내과학교실4 |
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| 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-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.
Key Words : Diabetic nephropathy, Proteinuria, Podocyte, Cyclosporin A, P-cadherin
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| Key Words:
Diabetic nephropathy, Proteinuria, Podocyte, Cyclosporin A0, P-cadherin |
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