Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy.
Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10(-8) M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RT-PCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immunohistochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats (P < 0.05), and colchicine treatment significantly reduced albuminuria in DM rats (P < 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney (P < 0.005), and this increase was significantly attenuated by Col treatment (P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.
Department of Internal Medicine, College of Medicine, Brain Korea 21 for Medical Science, Yonsei University, Seoul, Korea 120-752.
Jin Ji
JJ
Li
Sun Ha
SH
Lee
Dong Ki
DK
Kim
Ri
R
Jin
Dong-Sub
DS
Jung
Seung-Jae
SJ
Kwak
Seung Hye
SH
Kim
Seung Hyeok
SH
Han
Jung Eun
JE
Lee
Sung Jin
SJ
Moon
Dong-Ryeol
DR
Ryu
Tae-Hyun
TH
Yoo
Dae Suk
DS
Han
Shin-Wook
SW
Kang
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000187:drug effects / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013311:Streptozocin; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005353:Fibronectins; D012333:RNA, Messenger; D050257:Tubulin Modulators; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin; D003078:Colchicine