Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells

Background: Recent metabolomics studies have found circulatory metabolism alterations in patients with asthma, indicating that altered metabolites played a significant role in asthma. However, the regulatory mechanisms in asthma, especially in young chronic persistent asthma remain underexplored. Me...

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Autores principales: Bo Zhou, Gulinigaer Tuerhong Jiang, Hui Liu, Manyun Guo, Junhui Liu, Jianqing She
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:979eb8c185aa4c52bddc4821570b68672021-11-25T18:36:53ZDysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells10.3390/nu131141162072-6643https://doaj.org/article/979eb8c185aa4c52bddc4821570b68672021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4116https://doaj.org/toc/2072-6643Background: Recent metabolomics studies have found circulatory metabolism alterations in patients with asthma, indicating that altered metabolites played a significant role in asthma. However, the regulatory mechanisms in asthma, especially in young chronic persistent asthma remain underexplored. Methods: In this study, a prospective cohort of 162 patients diagnosed of asthma admitted to the First Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 was used to perform a nested case-control study. Among them, we included 30 patients with chronic persistent asthma between 20 to 35 years old; 30 health control with evenly distributed age and sex were then recruited. Nontargeted metabolomics was applied to identify serum metabolic profiles and altered metabolic pathways. Results: In vitro, human bronchial epithelial cells (HBECs) line BEAS-2B with the addition of L-citrulline and/or asymmetric dimethylarginine (ADMA) model was utilized and the concentrations of nitric oxide (NO) metabolites were tested to evaluate the therapeutic potential of L-citrulline. The young patients with chronic persistent asthma displayed dysregulated serum metabolic profiles, especially enriched in arginine metabolism. The ratio of L-citrulline to ornithine is associated with blood eosinophil count. In vitro, adding L-citrulline could reverse ADMA-mediated reduction of NOx at lower L-arginine concentration (25 μM), but was ineffective in the higher L-arginine concentration (100 μM) media. Conclusions: The arginine metabolism balance is of vital importance during the pathogenesis and progression of chronic asthma. L-citrulline could be a powerful approach to restore airway NO production, potentially exhibiting therapeutic benefits among young patients with chronic asthma.Bo ZhouGulinigaer Tuerhong JiangHui LiuManyun GuoJunhui LiuJianqing SheMDPI AGarticlechronic persistent asthmahuman airway epithelial cellsarginine metabolismL-citrullineNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4116, p 4116 (2021)
institution DOAJ
collection DOAJ
language EN
topic chronic persistent asthma
human airway epithelial cells
arginine metabolism
L-citrulline
Nutrition. Foods and food supply
TX341-641
spellingShingle chronic persistent asthma
human airway epithelial cells
arginine metabolism
L-citrulline
Nutrition. Foods and food supply
TX341-641
Bo Zhou
Gulinigaer Tuerhong Jiang
Hui Liu
Manyun Guo
Junhui Liu
Jianqing She
Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells
description Background: Recent metabolomics studies have found circulatory metabolism alterations in patients with asthma, indicating that altered metabolites played a significant role in asthma. However, the regulatory mechanisms in asthma, especially in young chronic persistent asthma remain underexplored. Methods: In this study, a prospective cohort of 162 patients diagnosed of asthma admitted to the First Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 was used to perform a nested case-control study. Among them, we included 30 patients with chronic persistent asthma between 20 to 35 years old; 30 health control with evenly distributed age and sex were then recruited. Nontargeted metabolomics was applied to identify serum metabolic profiles and altered metabolic pathways. Results: In vitro, human bronchial epithelial cells (HBECs) line BEAS-2B with the addition of L-citrulline and/or asymmetric dimethylarginine (ADMA) model was utilized and the concentrations of nitric oxide (NO) metabolites were tested to evaluate the therapeutic potential of L-citrulline. The young patients with chronic persistent asthma displayed dysregulated serum metabolic profiles, especially enriched in arginine metabolism. The ratio of L-citrulline to ornithine is associated with blood eosinophil count. In vitro, adding L-citrulline could reverse ADMA-mediated reduction of NOx at lower L-arginine concentration (25 μM), but was ineffective in the higher L-arginine concentration (100 μM) media. Conclusions: The arginine metabolism balance is of vital importance during the pathogenesis and progression of chronic asthma. L-citrulline could be a powerful approach to restore airway NO production, potentially exhibiting therapeutic benefits among young patients with chronic asthma.
format article
author Bo Zhou
Gulinigaer Tuerhong Jiang
Hui Liu
Manyun Guo
Junhui Liu
Jianqing She
author_facet Bo Zhou
Gulinigaer Tuerhong Jiang
Hui Liu
Manyun Guo
Junhui Liu
Jianqing She
author_sort Bo Zhou
title Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells
title_short Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells
title_full Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells
title_fullStr Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells
title_full_unstemmed Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells
title_sort dysregulated arginine metabolism in young patients with chronic persistent asthma and in human bronchial epithelial cells
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/979eb8c185aa4c52bddc4821570b6867
work_keys_str_mv AT bozhou dysregulatedargininemetabolisminyoungpatientswithchronicpersistentasthmaandinhumanbronchialepithelialcells
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AT huiliu dysregulatedargininemetabolisminyoungpatientswithchronicpersistentasthmaandinhumanbronchialepithelialcells
AT manyunguo dysregulatedargininemetabolisminyoungpatientswithchronicpersistentasthmaandinhumanbronchialepithelialcells
AT junhuiliu dysregulatedargininemetabolisminyoungpatientswithchronicpersistentasthmaandinhumanbronchialepithelialcells
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