Background Connective tissue disease (CTD) is a disease with a high incidence and a poor therapeutic effect. In recent years, in vitro and in vivo experimental studies have confirmed that the peroxisome proliferator-activated receptor γ (PPARγ) can interfere with the TGFβ1 pathway to play an anti-pulmonary fibrosis effect, but the exact mechanism is to be clarified.
Objectives To study the anti-fibrotic function and mechanism of PPARγ in connective tissue disease-interstitial lung disease (CTD-ILD).
Methods The expression of PPARγ in lungs was analyzed in 37 cases with CTD-ILD and 20 normal cases by immunohistochemistry. Changes in α-SMA levels were analyses by Western blot, and acetylation Smad3 and Smad3 or PPARγcombine with P300 were analysed by IP-WB. The data was analysed by One—Way ANOVA or t test.
Results PPARγ’expression in the lung of CTD-ILD is lower than the control ( 1.341±1.348% vs 3.923±1.978%, p<0.01 ). Different concentration of PPARγ(0, 1,5,10,20,40 ummol/l)ligand inhibited the marked elevation of the protein α-SMA induced by TGF-beta1 in a concentration-dependent manner(0.918±0.062 vs 0.852±0.042,0.725±0.057,0.678±0.042,0.418±0.022,0.456±0.029 ; P>0.05, P<0.05, P<0.01, P<0.01, P<0.01), this response was blocked by a selective antagonist of PPARγsignaling GW9662 ( 0.946+0.087 vs 0.538+0.120, P<0.01 ). Acetylation Smad3 expression was increased when TGFβ1 was putted into lung fibroblast after 60min, 90min and 180min ( 0.565±0.047, 1.127±0.101and 0.873±0.022 vs 0.614±0.407 ; all P<0.05 ) ) the combination of Smad3 with P300 was also increased ( 1.461±0.118 vs 0.982±0.094, P<0.05 ), but the ligand of PPAR γcan block the effect(P<0.05).
Conclusions PPARγmay play a physiologic role in the regulation of the anti-fibrosis response. Its function may be realized by its competition with Smad3 to combine with P300.
Kocheril S V, Appleton B E, Somers E C, et al. Comparison of disease progression and mortality of connective tissue disease-related interstitial lung disease and idiopathic interstitial pneumonia[J]. Arthritis Rheum, 2005,53(4):549-557.
Park J H, Kim D S, Park I N, et al. Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular disease-related subtypes[J]. Am J Respir Crit Care Med, 2007,175(7):705-711.
de Lauretis A, Veeraraghavan S, Renzoni E. Review series: Aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from IPF? How should the clinical approach differ?[J]. Chron Respir Dis, 2011,8(1):53-82.
Acknowledgements Thanks for my teacher xiaozhang, guangfengzhang
Disclosure of Interest None Declared
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