Proline is increased in allergic asthma and promotes airway remodeling
Tingting Xu, Zhenzhen Wu, Qi Yuan, Xijie Zhang, Yanan Liu, Chaojie Wu, Meijuan Song, Jingjing Wu, Jingxian Jiang, Zhengxia Wang, Zhongqi Chen, Mingshun Zhang, Mao Huang, Ningfei Ji
Tingting Xu, Zhenzhen Wu, Qi Yuan, Xijie Zhang, Yanan Liu, Chaojie Wu, Meijuan Song, Jingjing Wu, Jingxian Jiang, Zhengxia Wang, Zhongqi Chen, Mingshun Zhang, Mao Huang, Ningfei Ji
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Research Article Metabolism Pulmonology

Proline is increased in allergic asthma and promotes airway remodeling

Abstract

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 to our knowledge. In the present study, increased levels of plasma proline and PYCR1 were observed in patients with asthma. Similarly, proline and PYCR1 in lung tissues were high in a murine allergic asthma model induced by house dust mites (HDMs). Pycr1 knockout 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/mTORC1 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 exogenous proline 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.

Authors

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

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Figure 1

Metabolic profiling of plasma reveals altered amino acid levels in asthma.

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Metabolic profiling of plasma reveals altered amino acid levels in asthm...
(A) Heatmap of hierarchical clustering analysis of metabolite levels associated with organic acids for the control group (n = 8) and asthma group (n = 8) from the screening cohort. Hierarchical clustering analysis. (B) Bubble plot of enriched metabolites in KEGG pathways. (C) Metabolites associated with the proline metabolism pathway in the control group (n = 8) and asthma group (n = 8) from the screening cohort. Unpaired, 2-tailed Mann-Whitney test. (D) Plasma level of proline in the control group (n = 30) and asthma group (n = 34) from the validation cohort. Unpaired, 2-tailed Student’s t test. (E) Plasma level of PYCR1 in the control group (n = 30) and asthma group (n = 34) from the validation cohort. Unpaired, 2-tailed Student’s t test. (F) ROC curve of proline for asthma diagnosis. (G) ROC curve of PYCR1 for asthma diagnosis. (H) ROC curve of PYCR1 and proline for asthma diagnosis. Bar graphs and data are presented as the means ± SEMs. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.