RGD Reference Report - Telmisartan but not valsartan inhibits TGF-beta-mediated accumulation of extracellular matrix via activation of PPARgamma. - Rat Genome Database

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Telmisartan but not valsartan inhibits TGF-beta-mediated accumulation of extracellular matrix via activation of PPARgamma.

Authors: Yao, Y  Zou, R  Liu, X  Jiang, J  Huang, Q  He, Y  Li, M  Wang, S  Zhou, J  Ma, D  Xu, G 
Citation: Yao Y, etal., J Huazhong Univ Sci Technolog Med Sci. 2008 Oct;28(5):543-8. Epub 2008 Oct 10.
RGD ID: 2301867
Pubmed: PMID:18846335   (View Abstract at PubMed)
DOI: DOI:10.1007/s11596-008-0512-z   (Journal Full-text)

Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the suppression of mesangial cell activation is not fully understood. Since activation of peroxisome proliferators-activated receptor gamma (PPARgamma) has been proposed to decrease the effects of transforming growth factor-beta (TGF-beta) on glomerulosclerosis, we examined here whether and how telmisartan, an angiotensin II type 1 receptor blocker with PPARgamma-modulating activity, inhibited TGF-beta-induced glomerulosclerosis in rat glomerular mesangial cells. Protein levels of PPARgamma were detected by Western blot. Activation of PPARgamma response element (PPRE) was analyzed by luciferase assays. Deposition of extracelluar matrix was tested by confocol laser scanning. The results showed that telmisartan, but not valsartan, another angiotensin II type 1 receptor blocker, up-regulated PPARgamma protein levels in a dose-dependent manner (P<0.05). Activation of PPRE, represented by luciferase activity, was also increased with higher concentration of telmisartan in a dose-dependent manner (P<0.05). Furthermore, telmisartan inhibited TGF-beta-induced alpha-smooth muscle actin expression and collagen IV secretion in mesangial cells. GW9662, an inhibitor of PPAR-gamma, blocked the inhibitory effects of telmisartan on TGF-beta-induced glomerulosclerosis in mesangial cells. Our study indicates a benefit of telmisartan as a PPARgamma agonist against TGF-beta-induced mesangial cells activation in renal glomerulus. It may provide possibility that telmisartan works as a potential agent against diabetic nephropathy and hypertensive renal disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to xenobiotic stimulus  IEP 2301867 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pparg  (peroxisome proliferator-activated receptor gamma)


Additional Information