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Hospital Fund of China","award":["21JCQNJC00410"],"award-info":[{"award-number":["21JCQNJC00410"]}]},{"name":"Haihe Hospital Fund of China","award":["HHYY-202008"],"award-info":[{"award-number":["HHYY-202008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>(1) Background: Abnormal repair after alveolar epithelial injury drives the progression of idiopathic pulmonary fibrosis (IPF). The maintenance of epithelial integrity is based on the self-renewal and differentiation of alveolar type 2 (AT2) cells, which require sufficient energy. However, the role of glutamine metabolism in the maintenance of the alveolar epithelium remains unclear. In this study, we investigated the role of glutamine metabolism in AT2 cells of patients with IPF and in mice with bleomycin-induced fibrosis. (2) Methods: Single-cell RNA sequencing (scRNA-seq), transcriptome, and metabolomics analyses were conducted to investigate the changes in the glutamine metabolic pathway during pulmonary fibrosis. Metabolic inhibitors were used to stimulate AT2 cells to block glutamine metabolism. Regeneration of AT2 cells was detected using bleomycin-induced mouse lung fibrosis and organoid models. (3) Results: Single-cell analysis showed that the expression levels of catalytic enzymes responsible for glutamine catabolism were downregulated (p &lt; 0.001) in AT2 cells of patients with IPF, suggesting the accumulation of unusable glutamine. Combined analysis of the transcriptome (p &lt; 0.05) and metabolome (p &lt; 0.001) revealed similar changes in glutamine metabolism in bleomycin-induced pulmonary fibrosis in mice. Mechanistically, inhibition of the key enzymes involved in glucose metabolism, glutaminase-1 (GLS1) and glutamic-pyruvate transaminase-2 (GPT2) leads to reduced proliferation (p &lt; 0.01) and differentiation (p &lt; 0.01) of AT2 cells. (4) Conclusions: Glutamine metabolism is required for alveolar epithelial regeneration during lung injury.<\/jats:p>","DOI":"10.3390\/biom12050728","type":"journal-article","created":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T07:13:57Z","timestamp":1653203637000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Glutamine Metabolism Is Required for Alveolar Regeneration during Lung Injury"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0345-8941","authenticated-orcid":false,"given":"Sisi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-7912","authenticated-orcid":false,"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-9596","authenticated-orcid":false,"given":"Qingwen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-1415","authenticated-orcid":false,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-0535","authenticated-orcid":false,"given":"Huaiyong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin 300350, China"},{"name":"Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China"},{"name":"Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China"},{"name":"Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,22]]},"reference":[{"key":"ref_1","first-page":"204","article-title":"Control of satellite cell function in muscle regeneration and its disruption in ageing","volume":"23","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s41556-021-00734-6","article-title":"Identification of rare, transient post-mitotic cell states that are induced by injury and required for whole-body regeneration in Schmidtea mediterranea","volume":"23","author":"Brewster","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e21816","DOI":"10.1096\/fj.202100638R","article-title":"p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium","volume":"35","author":"Lorenzo","year":"2021","journal-title":"FASEB J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature25786","article-title":"Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor","volume":"555","author":"Zacharias","year":"2018","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Aspal, M., and Zemans, R.L. (2020). Mechanisms of ATII-to-ATI Cell Differentiation during Lung Regeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093188"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.yexcr.2016.04.006","article-title":"Role of mitochondrial hydrogen peroxide induced by intermittent hypoxia in airway epithelial wound repair in vitro","volume":"344","author":"Hamada","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1513\/pats.201201-010AW","article-title":"Stem Cells and Pulmonary Fibrosis: Cause or Cure?","volume":"9","author":"McNulty","year":"2012","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cell.2019.11.027","article-title":"Progressive Pulmonary Fibrosis Is Caused by Elevated Mechanical Tension on Alveolar Stem Cells","volume":"180","author":"Wu","year":"2020","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12931-014-0116-z","article-title":"Aging exacerbates damage and delays repair of alveolar epithelia following influenza viral pneumonia","volume":"15","author":"Yin","year":"2014","journal-title":"Respir. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"180077","DOI":"10.1183\/16000617.0077-2018","article-title":"The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype","volume":"27","author":"Olson","year":"2018","journal-title":"Eur. Respir. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1136\/annrheumdis-2020-217230","article-title":"Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)","volume":"80","author":"Spagnolo","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1056\/NEJMra003200","article-title":"Idiopathic Pulmonary Fibrosis","volume":"345","author":"Gross","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"580026","DOI":"10.3389\/fcell.2020.580026","article-title":"New Perspectives on the Aberrant Alveolar Repair of Idiopathic Pulmonary Fibrosis","volume":"8","author":"Tang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Baratella, E., Ruaro, B., Giudici, F., Wade, B., Santagiuliana, M., Salton, F., Confalonieri, P., Simbolo, M., Scarpa, A., and Tollot, S. (2021). Evaluation of Correlations between Genetic Variants and High-Resolution Computed Tomography Patterns in Idiopathic Pulmonary Fibrosis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11050762"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1126\/science.aam6603","article-title":"Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells","volume":"359","author":"Nabhan","year":"2018","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s41419-019-2111-2","article-title":"Airway epithelial regeneration requires autophagy and glucose metabolism","volume":"10","author":"Li","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1007\/s00018-021-03841-7","article-title":"Role and mechanisms of autophagy in lung metabolism and repair","volume":"78","author":"Li","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.stemcr.2020.01.008","article-title":"Autophagy Reprograms Alveolar Progenitor Cell Metabolism in Response to Lung Injury","volume":"14","author":"Li","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1089\/scd.2021.0050","article-title":"Effect of High Fat Diet on the Severity and Repair of Lung Fibrosis in Mice","volume":"30","author":"Hegab","year":"2021","journal-title":"Stem Cells Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1152\/jappl.1974.36.6.693","article-title":"Intracellular free amino acid concentration in human muscle tissue","volume":"36","author":"Vinnars","year":"1974","journal-title":"J. Appl. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41467-017-00369-y","article-title":"Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation","volume":"8","author":"Tan","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1007\/s00726-014-1773-4","article-title":"Glutamine and intestinal barrier function","volume":"47","author":"Wang","year":"2015","journal-title":"Amino Acids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1007\/s00726-016-2254-8","article-title":"The glutamine-alpha-ketoglutarate (AKG) metabolism and its nutritional implications","volume":"48","author":"Xiao","year":"2016","journal-title":"Amino Acids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.cmet.2019.01.016","article-title":"Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells","volume":"29","author":"Yu","year":"2019","journal-title":"Cell Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chen, Y., Tsai, Y.-H., Tseng, B.-J., and Tseng, S.-H. (2019). Influence of Growth Hormone and Glutamine on Intestinal Stem Cells: A Narrative Review. Nutrients, 11.","DOI":"10.3390\/nu11081941"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cllc.2013.09.001","article-title":"Altered Glutamine Metabolism and Therapeutic Opportunities for Lung Cancer","volume":"15","author":"Mohamed","year":"2014","journal-title":"Clin. Lung Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Vanhove, K., Derveaux, E., Graulus, G.-J., Mesotten, L., Thomeer, M., Noben, J.-P., Guedens, W., and Adriaensens, P. (2019). Glutamine Addiction and Therapeutic Strategies in Lung Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020252"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1165\/rcmb.2018-0179OC","article-title":"Pulmonary Neuroendocrine Cells Secrete \u03b3-Aminobutyric Acid to Induce Goblet Cell Hyperplasia in Primate Models","volume":"60","author":"Barrios","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1165\/rcmb.2017-0238OC","article-title":"Glutaminolysis Promotes Collagen Translation and Stability via \u03b1-Ketoglutarate\u2013mediated mTOR Activation and Proline Hydroxylation","volume":"58","author":"Ge","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/CM9.0000000000001086","article-title":"Sex-determining region Y-box 2-positive alveolar cells are responsive to bleomycin-induced lung injury","volume":"134","author":"Li","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaba1972","DOI":"10.1126\/sciadv.aba1972","article-title":"Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis","volume":"6","author":"Habermann","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41586-020-2922-4","article-title":"A molecular cell atlas of the human lung from single-cell RNA sequencing","volume":"587","author":"Travaglini","year":"2020","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5088","DOI":"10.1172\/JCI139519","article-title":"Contributions of alveolar epithelial cell quality control to pulmonary fibrosis","volume":"130","author":"Katzen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eaba1983","DOI":"10.1126\/sciadv.aba1983","article-title":"Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis","volume":"6","author":"Adams","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109482","DOI":"10.1016\/j.cellsig.2019.109482","article-title":"The leading role of epithelial cells in the pathogenesis of idiopathic pulmonary fibrosis","volume":"66","author":"Selman","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S2213-2600(18)30007-9","article-title":"Time for a change: Is idiopathic pulmonary fibrosis still idiopathic and only fibrotic?","volume":"6","author":"Wolters","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13059-019-1850-9","article-title":"A benchmark of batch-effect correction methods for single-cell RNA sequencing data","volume":"21","author":"Tran","year":"2020","journal-title":"Genome Biol."},{"key":"ref_40","first-page":"1370","article-title":"Network approaches to systems biology analysis of complex disease: Integrative methods for multi-omics data","volume":"19","author":"Yan","year":"2018","journal-title":"Brief Bioinform."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"624324","DOI":"10.3389\/fimmu.2021.624324","article-title":"Targeting SLC1A5 and SLC3A2\/SLC7A5 as a Potential Strategy to Strengthen Anti-Tumor Immunity in the Tumor Microenvironment","volume":"12","author":"Nachef","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"104844","DOI":"10.1016\/j.phrs.2020.104844","article-title":"Target the human Alanine\/Serine\/Cysteine Transporter 2(ASCT2): Achievement and Future for Novel Cancer Therapy","volume":"158","author":"Jiang","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1136\/gut.52.2.224","article-title":"Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate","volume":"52","author":"Clark","year":"2003","journal-title":"Gut"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"de Oliveira, G.P., Kitoko, J.Z., Lima-Gomes, P.D.S., Rochael, N.C., de Ara\u00fajo, C.C., Lugon, P.N., dos Santos, H.L., Martins, E.G.L., Ornellas, F.M., and de Oliveira, H.D. (2019). Glutamine Therapy Reduces Inflammation and Extracellular Trap Release in Experimental Acute Respiratory Distress Syndrome of Pulmonary Origin. Nutrients, 11.","DOI":"10.3390\/nu11040831"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"627842","DOI":"10.3389\/fmolb.2020.627842","article-title":"SARS-CoV-2 and Glutamine: SARS-CoV-2 Triggered Pathogenesis via Metabolic Reprograming of Glutamine in Host Cells","volume":"7","author":"Bharadwaj","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.freeradbiomed.2021.10.006","article-title":"Glutamine restores mitochondrial respiration in bleomycin-injured epithelial cells","volume":"176","author":"Shaghaghi","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1165\/rcmb.2019-0008OC","article-title":"Glutamine Metabolism Is Required for Collagen Protein Synthesis in Lung Fibroblasts","volume":"61","author":"Hamanaka","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/5\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:16:26Z","timestamp":1760138186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/5\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,22]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["biom12050728"],"URL":"https:\/\/doi.org\/10.3390\/biom12050728","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,22]]}}}