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

Korean Journal of Nephrology 2011;30(6):575-584.

Eun Jin Kim, M.D.1, Dong Ho Shin, M.D.1, Jin Ji Li, Ph.D.2, Sun Ha Lee, Ph.D.1, Yong Kang Lee, M.D.1, Hee-Jin Park, M.D.1, Hannah Seok, M.D.1, Jung Tak Park, M.D.1, Seung Hyeok Han, M.D.1, Tae-Hyun Yoo, M.D.1 and Shin-Wook Kang, M.D.1

Department of Internal Medicine¹
College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 for Medical Science, Yonsei University, Seoul, Korea Nephrology and Dialysis Unit, Department of Internal Medicine²
The Affiliated Hospital, YanBian University Medical College, JiLin, China

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

Department of Internal Medicine1, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 for Medical Science, Yonsei University, Seoul, Korea Nephrology and Dialysis Unit, Department of Internal Medicine2, The Affiliated Hospital, Yan

Abstract

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.

Key Words: Colchicine, Diabetic nephropathy, Renin-angiotensin system, ICAM-1, Fibronectin