RGD Reference Report - Telmisartan improves kidney function through inhibition of the oxidative phosphorylation pathway in diabetic rats. - Rat Genome Database

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Telmisartan improves kidney function through inhibition of the oxidative phosphorylation pathway in diabetic rats.

Authors: Zhang, Qian  Xiao, Xinhua  Li, Ming  Li, Wenhui  Yu, Miao  Zhang, Huabing  Sun, Xiaofang  Mao, Lili  Xiang, Hongding 
Citation: Zhang Q, etal., J Mol Endocrinol. 2012 Jun 26;49(1):35-46. doi: 10.1530/JME-12-0020. Print 2012 Aug.
RGD ID: 13792578
Pubmed: PMID:22591908   (View Abstract at PubMed)
DOI: DOI:10.1530/JME-12-0020   (Journal Full-text)

Telmisartan provides renal benefit at all stages of the renal continuum in patients with type 2 diabetes mellitus. This research is to investigate the effect of telmisartan on kidney function in diabetic rats and to identify the underlying molecular mechanisms. Diabetic rats were divided into vehicle group, low dosage (TeL) group, and high dosage of telmisartan (TeH) group. We performed Illumina RatRef-12 Expression BeadChip gene array experiments. We found 3-months of treatment with telmisartan significantly decreased 24-h urinary albumin, serum creatinine, blood urea nitrogen, and increased creatinine clearance rate. Kidney hypertrophy and glomerular mesangial matrix expansion were ameliorated. The glomeruli from the TeH group had 1541 genes with significantly changed expression (554 increased, 987 decreased). DAVID (Database for annotation, visualization and Integrated discovery) analyses showed that the most enriched term was 'mitochondrion' (Gene Ontology (GO:0005739)) in all 67 GO functional categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that all differentially expressed genes included seven KEGG pathways. Of those pathways, four are closely related to the oxidative phosphorylation pathway. Quantitative real-time PCR verified that the H+ transporting mitochondrial F1 complex, beta subunit (Atp5b), cytochrome c oxidase subunit VIc (Cox6c), and NADH dehydrogenase (ubiquinone) Fe-S protein 3 (Ndufs3) were significantly downregulated both in TeL and TeH groups, while nephrosis 1 homolog (Nphs1) and nephrosis 2 homolog (Nphs2) were significantly upregulated. The increased expression of malonaldehyde and NDUFS3 in the glomeruli of diabetic rats was attenuated by telmisartan. The other significantly changed pathway we found was the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our data suggest that telmisartan can improve kidney function in diabetic rats. The mechanism may be involved in mitochondrion oxidative phosphorylation, the PPAR-γ pathway, and the slit diaphragm.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATP5F1BHumanDiabetic Nephropathies treatmentISORGD:621368mRNA:decreased expression:renal glomerulus (rat)RGD 
Atp5f1bRatDiabetic Nephropathies treatmentIDA mRNA:decreased expression:renal glomerulus (rat)RGD 
Atp5f1bMouseDiabetic Nephropathies treatmentISORGD:621368mRNA:decreased expression:renal glomerulus (rat)RGD 
NDUFS3HumanDiabetic Nephropathies treatmentISORGD:1309406associated with Diabetes Mellitus, Experimental RGD 
Ndufs3RatDiabetic Nephropathies treatmentIEP associated with Diabetes Mellitus, Experimental RGD 
Ndufs3MouseDiabetic Nephropathies treatmentISORGD:1309406associated with Diabetes Mellitus, Experimental RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp5f1b  (ATP synthase F1 subunit beta)
Ndufs3  (NADH:ubiquinone oxidoreductase core subunit S3)

Genes (Mus musculus)
Atp5f1b  (ATP synthase F1 subunit beta)
Ndufs3  (NADH:ubiquinone oxidoreductase core subunit S3)

Genes (Homo sapiens)
ATP5F1B  (ATP synthase F1 subunit beta)
NDUFS3  (NADH:ubiquinone oxidoreductase core subunit S3)


Additional Information