Korean J Nephrol.  2011 Nov;30(6):575-584.

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

• Kim EJ
• Shin DH
• Li JJ
• Lee SH
• Lee YK
• Park HJ
• Seok H
• Park JT
• Han SH
• Yoo TH
• Kang SW

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.

Keyword

Colchicine; Diabetic nephropathy; Renin-angiotensin system; ICAM-1; Fibronectin

MeSH Terms

Angiotensin II
Angiotensins
Animals
Blotting, Western
Colchicine
Culture Media, Conditioned
Diabetic Nephropathies
Fibronectins
Glucose
Imidazoles
Intercellular Adhesion Molecule-1
Leukocytes
Mesangial Cells
Rats
Real-Time Polymerase Chain Reaction
Renin-Angiotensin System
RNA, Messenger
Tetrazoles
Angiotensin II
Angiotensins
Colchicine
Culture Media, Conditioned
Fibronectins
Glucose
Imidazoles
Intercellular Adhesion Molecule-1
RNA, Messenger
Tetrazoles