PPARγ agonists inhibit TGF-β-PKA signaling in glomerulosclerosis

Abstract

Aim: To study the probable mechanisms of the anti-glomerulosclerosis effects induced by peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ agonist, either troglitazone or telmisartan, for the indicated times. Promega luciferase assays were subsequently used for the detection of PPARγ 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 α-smooth muscle actin (α-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-β. The PPARγ agonists also inhibited α-SMA and collagen IV protein expression by blocking PKA activation. Conclusion: PPARγ ligands effectively suppress the activation of MCs and the accumulation of collagen IV stimulated by TGF-β in vitro. The renal protection provided by PPARγ agonists is partly mediated via their blockade of TGF-β/PKA signaling.

Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)

“…47 The findings in the present study suggest that PPAR-γ agonist (pioglitazone) could be a potential therapeutic agent for RA.…”

PPARγRegulates Genes Involved in Triacylglycerol Synthesis and Secretion in Mammary Gland Epithelial Cells of Dairy Goats

“…Binding of ligands to the PPAR γ ligand binding domain causes conformational changes in the receptor [16, 19]. Once activated, PPAR γ forms a heterodimeric complex with retinoid X receptor (RXR) and binds to the PPRE upstream of target genes [8]. In the present study, dairy goat mammary epithelial cells were incubated with rosiglitazone, a chemosynthetic ligand, which has a high affinity for PPAR γ and enhanced its activity.…”

“…The luciferase vector (pGL3-basic) containing three copies of PPRE was designed as described before [8]. The shRNA sequences were designed using the WI siRNA Selection Program (http://sirna.wi.mit.edu/home.php) and BLOCK-iT RNAi Designer (http://rnaidesigner.invitrogen.com/rnaiexpress/) using the goat PPAR γ gene sequence (HQ589347.1).…”

Transcriptome-Wide Analysis Reveals the Role of PPARγControlling the Lipid Metabolism in Goat Mammary Epithelial Cells

“…After binding of ligands (e.g., rosiglitazone (ROSI) or pioglitazone), PPARG causes conformational changes in the receptor [7, 8] and then forms a heterodimeric complex with RXR proteins and binds to PPAR response element (PPRE) upstream of target genes [9]. Through controlling the downstream genes, PPARG regulates adipocyte differentiation and promotes insulin sensitivity in human and rodents [7].…”