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Colchicine Ameliorates High Glucose-Induced ICAM-1 and Fibronectin Expression in Renal Cells via Inhibiting Locally-Produced Angiotensin II.

 Eun Jin Kim  ;  Dong Ho Shin  ;  Shin-Wook Kang  ;  Tae-Hyun Yoo  ;  Seung Hyeok Han  ;  Jung Tak Park  ;  Hannah Seok  ;  Hee-Jin Park  ;  Yong Kang Lee  ;  Sun Ha Lee  ;  Jin Ji Li 
 Korean Journal of Nephrology, Vol.30(6) : 575-584, 2011 
Journal Title
 Korean Journal of Nephrology 
Issue Date
PURPOSE: A previous study has demonstrated that colchicine abrogated intercellular adhesion molecule (ICAM)-1 and fibronectin expression in renal cells exposed to high glucose media, but the underlying mechanism was not clarified. This study was undertaken to elucidate whether it was attributed to the inhibitory effect of colchicine on locally-produced angiotensin II (AII) under diabetic conditions. METHODS: Rat mesangial cells and NRK-52E cells were cultured in media containing 5.6 mM glucose (NG), NG+10(-7) M AII (NG+AII), or 30 mM glucose (HG) with or without 10(-8) M colchicine (Col) and/or 10(-6) M L-158,809, an AII type 1 receptor blocker (ARB). ICAM-1 and fibronectin mRNA and protein expressions were determined by real-time PCR (RT-PCR) and Western blot, respectively. AII levels in conditioned media were determined by ELISA. RESULTS: AII levels in conditioned media were significantly higher in HG-stimulated mesangial cells and NRK-52E cells compared to NG cells (p<0.05). ICAM-1 and fibronectin mRNA and protein expression were significantly increased in renal cells exposed to HG media (p<0.05 or p<0.01), and these increases were significantly ameliorated by colchicine or ARB treatment (p<0.05). Colchicine and ARB also significantly attenuated AII-induced ICAM-1 and fibronectin expression (p<0.05). However, there was no additive inhibitory effect of colchicine and ARB on the increases in ICAM-1 and fibronectin expression. CONCLUSION: Colchicine abrogated increased ICAM-1 and fibronectin expression in renal cells under diabetic conditions, which is partly mediated by inhibiting HG-induced locally-produced AII. These findings provide a new renoprotective mechanism of colchicine in diabetic nephropathy in addition to its impact on leukocyte functions
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
강신욱(Kang, Shin Wook) ; 김은진(Kim, Eun Jin) ; 박정탁(Park, Jung Tak) ; 박희진(Park, Hee Jin) ; 석한나(Seok, Hannah) ; 신동호(Shin, Dong Ho) ; 유태현(Yoo, Tae Hyun) ; 이용강(Lee, Yong Kang) ; 한승혁(Han, Seung Hyeok)
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