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 4

HDM extract promotes proline elevation and PYCR1 expression in bronchial alveolar epithelial cells.

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HDM extract promotes proline elevation and PYCR1 expression in bronchial...
(A) The level of proline in HDM-stimulated MLE-12 cells for 24 hours was measured by the colorimetric method. (B) The level of PYCR1 in MLE-12 cells was identified as costained with DAPI (blue) and PYCR1 (red) and observed by microscopy; original magnification 400×; scale bar, 50 μm. (C) Western blot analysis of PYCR1 expression in MLE-12 cells treated with HDM extract (100 μg/mL). (D) Western blot analysis of PYCR1 expression in BEAS-2B cells treated with HDM extract (100 μg/mL). (E) Western blot analysis of E-cadherin expression in primary tracheal epithelial cells treated with HDM extract from WT mice and Pycr1-KO mice (100 μg/mL) for 24 hours. Bar graphs and data are presented as the means ± SEMs. Group comparisons were made using 2-tailed Student’s t test (A) and paired 1-way ANOVA (C–E) followed by Bonferroni’s post hoc test. The results are from at least 3 independent experiments. *P < 0.05, **P < 0.01.