The anti-fibrosis mechanism of peroxisome proliferator activated receptor γ in connective tissue disease related interstitial lung disease / 中华风湿病学杂志

ABSTRACT

Objective To study the anti-fibrotic function and mechanism of peroxisome proliferator activated receptorγ(PPARγ) in connective tissue disease-interstitial lung disease (CTD-ILD).Methods The expression of PPARγin lungs was analyzed in 37 cases with CTD-ILD and 20 control cases by immunohistochemistry.Changes in α-SMA levels were analyzed by Western blotting,and acetylation of Smad3 and Smad3 or PPARγ combined with P300 were analyzed by IP-WB.The data was analyzed by one-way ANOVA,t test or Mann-Whitney test.Results PPARγ' expression in the lung of CTD-ILD was lower than the controls [0.92％(1.44％),3.50％(1.94)％,respectively; Z=-8.924,P＜0.01].Different concentration of PPARγ (0,1,5,10,20,40 pmol/L) ligandinhibited the marked elevation of the protein α-SMA induced by TGF-β1 in a concentration-dependent manner (0.918 ±0.062,0.852±0.042,0.725 ±0.057,0.678 ±0.042,0.418 ±0.022,0.456±0.029; P＜0.05 or P＜0.01).However,this response was blocked by a selective antagonist PPARγ signaling GW9662 (0.946±0.087 vs 0.538±0.120,P＜0.01).Acetylation of Smad3 expression was increased when TGF-β1 was putted into lung fibroblasts after 60,90 and 180 min (0.565±0.047,1.127±0.101,0.873±0.022,0.614±0.407; all P＜0.05).The combination of Smad3 with P300 was also increased (1.46±0.12,0.98±0.09; P＜0.05),compared with the controls.But the ligand of PPARγ could block this effect (0.62±0.10,1.46±0.12; P＜0.05).Meanwhile,the combination of PPARγ and P300 was increased (0.94±0.05,0.76±0.22; P＜0.05).Conclusion PPARγ may play a physiologic role in the regulation of anti-fibrosis response.Its function may be realized by its competition with Smad3 combined with P300.