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THU0486 Peroxisome Proliferator Activated Receptorγ Anti-Fibrosis Mechanism in Connective Tissue Disease Related Interstitial Lung Disease
  1. X. Pan1,
  2. X. zhang2,
  3. G. zhang3
  1. 1Rheumatism Immunity Branch, Guang Dong Province People’s Hospital
  2. 2Rheumatism Immunity Branch, Guang Dong Province Pepole’s Hospital
  3. 3Rheumatism Immunity Branch, Guang Dong Province Hospital, Guang Zhou, China

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

  1. 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.

  2. 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.

  3. 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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