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Acta Pharmacol Sin 2010, PMID: 20037602

PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis.

Zou, Rong; Xu, Gang; Liu, Xiao-cheng; Han, Min; Jiang, Jing-jing; Huang, Qian; He, Yong; Yao, Ying

OBJECTIVE

To study the probable mechanisms of the anti-glomerulosclerosis effects induced by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists in rat intraglomerular mesangial cells (MCs).

METHODS

Cells were transfected with the pTAL-PPRE-tk-Luc(+) plasmid and then treated with different concentrations of PPARgamma agonist, either troglitazone or telmisartan, for the indicated times. Promega luciferase assays were subsequently used for the detection of PPARgamma activation. Protein expression levels were assessed by Western blot, and PepTag assays were used for the non-radioactive detection of protein kinase A (PKA) activity. The deposition of alpha-smooth muscle actin (alpha-SMA) and p-cyclic AMP responsive element binding protein (pCREB) were analyzed by confocal laser scanning.

RESULTS

Both troglitazone and telmisartan remarkably inhibit the PKA activation and pCREB expression that is stimulated by TGF-beta. The PPARgamma agonists also inhibited alpha-SMA and collagen IV protein expression by blocking PKA activation.

CONCLUSIONS

PPARgamma ligands effectively suppress the activation of MCs and the accumulation of collagen IV stimulated by TGF-beta in vitro. The renal protection provided by PPARgamma agonists is partly mediated via their blockade of TGF-beta/PKA signaling.

Diseases/Pathways annotated by Medline MESH: Glomerulonephritis
Document information provided by NCBI PubMed

Text Mining Data

alpha-SMA → PKA: " The PPARgamma agonists also inhibited alpha-SMA and collagen IV protein expression by blocking PKA activation "

collagen IV → PKA: " The PPARgamma agonists also inhibited alpha-SMA and collagen IV protein expression by blocking PKA activation "

Manually curated Databases

No curated data.