RGD Reference Report - Colchicine Attenuates Inflammatory Cells Infiltration and Extracellular Matrix Accumulation in Diabetic Nephropathy. - Rat Genome Database

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Colchicine Attenuates Inflammatory Cells Infiltration and Extracellular Matrix Accumulation in Diabetic Nephropathy.

Authors: Li, JJ  Lee, SH  Kim, DK  Jin, R  Jung, DS  Kwak, SJ  Kim, SH  Han, SH  Lee, JE  Moon, SJ  Ryu, DR  Yoo, TH  Han, DS  Kang, SW 
Citation: Li JJ, etal., Am J Physiol Renal Physiol. 2009 Apr 15.
RGD ID: 2306980
Pubmed: PMID:19369290   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.90649.2008   (Journal Full-text)

Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine 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, sixty-four 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 blot 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-week and 3-month were significantly higher in DM compared to 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 to C kidney (p<0.005), and this increase was significantly attenuated by Col treatment (p<0.01). In conclusion, Col prevents not only inflammatory cells 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. Key words: Colchicine, Diabetic nephropathy, inflammation, MCP-1, fibronectin.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  ISOCcl2 (Rattus norvegicus)2306980; 2306980associated with Diabetes Mellitus more ...RGD 
Diabetic Nephropathies  IEP 2306980associated with Diabetes Mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information