哮喘
炎症
脯氨酸
过敏
气道
免疫学
癌症研究
化学
医学
氨基酸
生物化学
外科
作者
Tingting Xu,Zhenzhen Wu,Qing Yuan,Xijie Zhang,Yanan Liu,Chaojie Wu,Ming Song,Jingjing Wu,Jingxian Jiang,Zhengxia Wang,Zhongqi Chen,Mingshun Zhang,Mao Huang,Ningfei Ji
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2023-08-22
卷期号:8 (16)
被引量:1
标识
DOI:10.1172/jci.insight.167395
摘要
Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1 function in allergic asthmatic airway remodeling via EMT has not yet been addressed. In the present study, increased levels of plasma proline and PYCR1 were observed in asthmatic patients. Similarly, proline and PYCR1 in lung tissues were higher in a murine allergic asthma model induced by house dust mites (HDMs). Pycr1 knockout (KO) decreased proline in lung tissues, with reduced airway remodeling and EMT. Mechanistically, loss of Pycr1 restrained HDM-induced EMT by modulating mitochondrial fission, metabolic reprogramming, and the AKT/mTOR1 and WNT3a/β–catenin signaling pathways in airway epithelial cells. Therapeutic inhibition of PYCR1 in wild-type mice disrupted HDM-induced airway inflammation and remodeling. Deprivation of exogeneous proline partially relieved HDM-induced airway remodeling to some extent. Collectively, this study illuminates that proline and PYCR1 involved with airway remodeling in allergic asthma could be viable targets for asthma treatment.
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