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过氧化物酶体增殖物激活受体 γ 作为治疗慢性气道炎症性疾病气道黏液高分泌的潜在靶点。

PPARγ as a Potential Target to Treat Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases.

机构信息

Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

PPAR Res. 2012;2012:256874. doi: 10.1155/2012/256874. Epub 2012 Jun 17.

Abstract

Airway mucus hypersecretion (AMH) is a key pathophysiological feature of chronic airway inflammatory diseases such as bronchial asthma, cystic fibrosis, and chronic obstructive pulmonary disease. AMH contributes to the pathogenesis of chronic airway inflammatory diseases, and it is associated with reduced lung function and high rates of hospitalization and mortality. It has been suggested that AMH should be a target in the treatment of chronic airway inflammatory diseases. Recent evidence suggests that a key regulator of airway inflammation, hyperresponsiveness, and remodeling is peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcription factor that regulates adipocyte differentiation and lipid metabolism. PPARγ is expressed in structural, immune, and inflammatory cells in the lung. PPARγ is involved in mucin production, and PPARγ agonists can inhibit mucin synthesis both in vitro and in vivo. These findings suggest that PPARγ is a novel target in the treatment of AMH and that further work on this transcription factor may lead to new therapies for chronic airway inflammatory diseases.

摘要

气道黏液高分泌(AMH)是支气管哮喘、囊性纤维化和慢性阻塞性肺疾病等慢性气道炎症性疾病的一个关键病理生理特征。AMH 促进了慢性气道炎症性疾病的发病机制,与肺功能下降、住院率和死亡率升高有关。有人提出,AMH 应该成为慢性气道炎症性疾病治疗的靶点。最近的证据表明,过氧化物酶体增殖物激活受体 γ(PPARγ)是气道炎症、高反应性和重塑的关键调节因子,它是一种配体激活的转录因子,可调节脂肪细胞分化和脂质代谢。PPARγ 在肺的结构、免疫和炎症细胞中表达。PPARγ 参与黏蛋白的产生,PPARγ 激动剂可以在体外和体内抑制黏蛋白的合成。这些发现表明,PPARγ 是治疗 AMH 的一个新靶点,对该转录因子的进一步研究可能为慢性气道炎症性疾病带来新的治疗方法。

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