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Proline is increased in allergic asthma and promotes airway remodeling

by Wang, Zhengxia , Wu, Zhenzhen , Xu, Tingting , Wu, Jingjing , Jiang, Jingxian , Zhang, Mingshun , Liu, Yanan , Song, Meijuan , Chen, Zhongqi , Huang, Mao , Ji, Ningfei , Wu, Chaojie , Zhang, Xijie , Yuan, Qi

in AKT protein / Allergens / Allergies / Asthma / Biomarkers / Carboxylate reductase / Collagen / Enzymes / Epithelial cells / Growth factors / Medical diagnosis / Metabolism / Metabolites / Plasma / Proline / Pulmonology / Pyrroline-5-carboxylate reductase / Respiratory tract diseases / Smooth muscle / β-Catenin

2023

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Proline is increased in allergic asthma and promotes airway remodeling

2023

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2023

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Journal Article

Proline is increased in allergic asthma and promotes airway remodeling

Wang, Zhengxia,

Wu, Zhenzhen,

Xu, Tingting,

Wu, Jingjing,

Jiang, Jingxian,

Zhang, Mingshun,

Liu, Yanan,

Song, Meijuan,

Chen, Zhongqi,

Huang, Mao,

Ji, Ningfei,

Wu, Chaojie,

Zhang, Xijie,

Yuan, Qi

2023

Overview

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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Publisher

American Society for Clinical Investigation,American Society for Clinical investigation

Subject

/ Asthma

/ Carboxylate reductase

/ Collagen