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 2

PYCR1 gene expression is increased in the airway epithelium of patients with asthma compared with healthy controls.

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PYCR1 gene expression is increased in the airway epithelium of patients...
(A) Box plots of PYCR1 gene expression in airway epithelial cells from individuals in GSE67472 (n control = 43 and n asthma = 62). (B) Box plots of PYCR1 gene expression in airway epithelial cells from individuals in GSE179156 (n control = 29, n asthma = 57). (C) Box plots of PYCR1 gene expression in airway epithelial cells from individuals in GSE43696 (n control = 20, n asthma = 88). (D) Box plots of PYCR1 gene expression in airway epithelial cells from individuals in GSE63142 (n control = 27, n asthma = 128). (E) Box plots of PYCR1 gene expression in airway epithelial cells from individuals in GSE67940 (n mild-moderate = 43, n severe = 30). (F) Box plots of PYCR1 gene expression in airway epithelial cells from individuals in GSE76226 (n moderate = 36, n severe = 63). Bar graphs and data are presented as medians ± IQRs. Results are shown as box-and-whisker plots. (The middle horizontal line within the box represents the median, boxes extend from the 25th to the 75th percentiles, and the whiskers represent 95% CIs.) Statistical differences were determined with an unpaired, 2-tailed Wilcoxon rank-sum test. *P < 0.05, **P < 0.01, ***P < 0.001.