RGD Reference Report - Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. - Rat Genome Database

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Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats.

Authors: Ko, GJ  Kang, YS  Han, SY  Lee, MH  Song, HK  Han, KH  Kim, HK  Han, JY  Cha, DR 
Citation: Ko GJ, etal., Nephrol Dial Transplant. 2008 Sep;23(9):2750-60. Epub 2008 Apr 3.
RGD ID: 2301862
Pubmed: PMID:18388116   (View Abstract at PubMed)
DOI: DOI:10.1093/ndt/gfn157   (Journal Full-text)

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in insulin sensitivity, lipid metabolism and inflammation. However, the effects of PPARgamma agonist on renal inflammation have not been fully examined in type 2 diabetic nephropathy. METHODS: In the present study, we investigated the effect and molecular mechanism of the PPARgamma agonist, pioglitazone, on the progression of diabetic nephropathy in type 2 diabetic rats. Inflammatory markers including NF-kappaB, MCP-1 and pro-fibrotic cytokines were determined by RT-PCR, western blot, immunohistochemical staining and EMSA. In addition, to evaluate the direct anti-inflammatory effect of PPARgamma agonist, we performed an in vitro study using mesangial cells. RESULTS: Treatment of OLETF rats with pioglitazone improved insulin sensitivity and kidney/body weight, but had a little effect on blood pressure. Pioglitazone treatment markedly reduced urinary albumin and MCP-1 excretion, and ameliorated glomerulosclerosis. In cDNA microarray analysis using renal cortical tissues, several inflammatory and profibrotic genes were significantly down-regulated by pioglitazone including NF-kappaB, CCL2, TGFbeta1, PAI-1 and VEGF. In renal tissues, pioglitazone treatment significantly reduced macrophage infiltration and NF-kappaB activation in association with a decrease in type IV collagen, PAI-1, and TGFbeta1 expression. In cultured mesangial cells, pioglitazone-activated endogenous PPARgamma transcriptional activity and abolished high glucose-induced collagen production. In addition, pioglitazone treatment also markedly suppressed high glucose-induced MCP-1 synthesis and NF-kappaB activation. CONCLUSIONS: These data suggest that pioglitazone not only improves insulin resistance, glycaemic control and lipid profile, but also ameliorates renal injury through an anti-inflammatory mechanism in type 2 diabetic rats.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPARGHumanDiabetic Nephropathies  ISOPparg (Rattus norvegicus)associated with Diabetes Mellitus and Non-Insulin-DependentRGD 
PpargRatDiabetic Nephropathies  IMP associated with Diabetes Mellitus and Non-Insulin-DependentRGD 
PpargMouseDiabetic Nephropathies  ISOPparg (Rattus norvegicus)associated with Diabetes Mellitus and Non-Insulin-DependentRGD 
CCL2Humantype 2 diabetes mellitus  ISOCcl2 (Rattus norvegicus)protein:increased expression:urineRGD 
Ccl2Rattype 2 diabetes mellitus  IEP protein:increased expression:urineRGD 
Ccl2Mousetype 2 diabetes mellitus  ISOCcl2 (Rattus norvegicus)protein:increased expression:urineRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ccl2Ratresponse to xenobiotic stimulus  IEP pioglitazoneRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)
Pparg  (peroxisome proliferator-activated receptor gamma)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)
Pparg  (peroxisome proliferator activated receptor gamma)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)
PPARG  (peroxisome proliferator activated receptor gamma)

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

Additional Information