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Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy

Authors
 Jin Ji Li  ;  Sun Ha Lee  ;  Dong Ki Kim  ;  Ri Jin  ;  Dong-Sub Jung  ;  Seung-Jae Kwak  ;  Seung Hye Kim  ;  Seung Hyeok Han  ;  Jung Eun Lee  ;  Sung Jin Moon  ;  Dong-Ryeol Ryu  ;  Tae-Hyun Yoo  ;  Dae Suk Han  ;  Shin-Wook Kang 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, Vol.297(1) : 200-9, 2009 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 
ISSN
 1931-857X 
Issue Date
2009
MeSH
Animals ; Cell Movement/drug effects* ; Cells, Cultured ; Chemokine CCL2/drug effects ; Chemokine CCL2/metabolism ; Colchicine/pharmacology* ; Colchicine/therapeutic use ; Diabetes Mellitus, Experimental/complications* ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/metabolism* ; Diabetic Nephropathies/pathology* ; Disease Models, Animal ; Extracellular Matrix/drug effects ; Extracellular Matrix/metabolism* ; Fibronectins/metabolism ; Inflammation/pathology* ; Intercellular Adhesion Molecule-1/drug effects ; Intercellular Adhesion Molecule-1/metabolism ; Macrophages/drug effects ; Macrophages/pathology ; RNA, Messenger/metabolism ; Rats ; Streptozocin ; Tubulin Modulators/pharmacology* ; Tubulin Modulators/therapeutic use
Keywords
inflammation ; MCP-1 ; ICAM-1 ; fibronectin ; afferent arteriole ; contraction ; losartan
Abstract
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
Files in This Item:
T200903116.pdf Download
DOI
10.1152/ajprenal.90649.2008
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Jung Eun(이정은) ORCID logo https://orcid.org/0000-0003-0917-2872
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104699
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