THU0486 Peroxisome Proliferator Activated Receptorγ Anti-Fibrosis Mechanism in Connective Tissue Disease Related Interstitial Lung Disease. (23rd January 2014)

• Record Type: Journal Article
• Authors: Pan, X.; zhang, X.; zhang, G.
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 3(2013)
• Page Start: A328
• Page End: A328
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-eular.1014
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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. References: 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