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KMID : 0359920110300060575
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Korean Journal of Nephrology
2011 Volume.30 No. 6 p.575 ~ p.584
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Colchicine Ameliorates High Glucose-Induced ICAM-1 and Fibronectin Expression in Renal Cells via Inhibiting Locally-Produced Angiotensin II
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Kim Eun-Jin
Shin Dong-Ho
Li Jin-Ji
Lee Sun-Ha
Lee Yong-Kang
Park Hee-Jin
Seok Han-Nah
Park Jung-Tak
Han Seung-Hyeok
Yoo Tae-Hyun
Kang Shin-Wook
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Abstract
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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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KEYWORD
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Colchicine, Diabetic nephropathy, Renin-angiotensin system, ICAM-1, Fibronectin
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