{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:49:27Z","timestamp":1791607767131,"version":"4.3.4"},"reference-count":73,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States Department of War","award":["HT9525-23-1-0372"],"award-info":[{"award-number":["HT9525-23-1-0372"]}]},{"name":"United States Department of War","award":["W81XWH211 0414"],"award-info":[{"award-number":["W81XWH211 0414"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The potent redox-cycling Pseudomonas aeruginosa secondary metabolite pyocyanin induces acute and persistent oxidative stress in diseased airways. Pyocyanin promotes goblet cell hyperplasia and metaplasia and exacerbates the mucus burden. Forkhead Box A2 (FOXA2) is a key pioneer factor that governs the transition of airway basal epithelial and club cells to goblet cells by transcriptionally repressing the expression of MUC5AC and MUC5B mucin genes. FOXA2 activity is negatively regulated by Thr156 phosphorylation in various cell types. However, how post-translational modifications modulate the transcriptional repression of FOXA2 on airway mucin genes remains uncharacterized. Here, we demonstrate that the interaction between SIRT1 and FOXA2 is significantly increased within pyocyanin-exposed MUC5AC-expressing human bronchial epithelial cells, and in human COPD and pyocyanin-exposed mouse lungs. Pyocyanin promotes SIRT1-mediated deacetylation of FOXA2, which serves as a prerequisite for subsequent phosphorylation, inactivation, and MUC5AC derepression. Specifically, under pyocyanin-imposed oxidative stress, SIRT1 deacetylates FOXA2 at Lys259, which dictates phosphorylation at Thr156, leading to nuclear exclusion, ubiquitination, and proteasome-mediated degradation, initiating airway goblet cell transdifferentiation. By contrast, inactivation of SIRT1 by transient knockdown and chemical inhibition impedes pyocyanin-induced FOXA2 phosphorylation and MUC5AC expression. Our results uncover a novel role of SIRT1 in regulating FOXA2 expression dynamics governing airway mucus homeostasis.<\/jats:p>","DOI":"10.3390\/ijms27198882","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:28:05Z","timestamp":1791296885000},"page":"8882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pseudomonas aeruginosa Pyocyanin Increases Airway Mucin Biosynthesis by SIRT1-Mediated FOXA2 Inactivation"],"prefix":"10.3390","volume":"27","author":[{"given":"Woosuk","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Kosmider","sequence":"additional","affiliation":[{"name":"Center for Inflammation and Lung Research, Department of Microbiology, Immunology and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gee W.","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a028241","DOI":"10.1101\/cshperspect.a028241","article-title":"Cilia and mucociliary clearance","volume":"9","author":"Ostrowski","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_2","first-page":"139","article-title":"Clinical issues of mucus accumulation in COPD","volume":"9","author":"Ramos","year":"2014","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a009589","DOI":"10.1101\/cshperspect.a009589","article-title":"CFTR, mucins, and mucus obstruction in cystic fibrosis","volume":"2","author":"Kreda","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1164\/rccm.201303-0411CI","article-title":"Non\u2013cystic fibrosis bronchiectasis","volume":"188","author":"McShane","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1164\/rccm.201906-1219OC","article-title":"Airway mucus hyperconcentration in non\u2013cystic fibrosis bronchiectasis","volume":"201","author":"Ramsey","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1056\/NEJMoa1701632","article-title":"Airway mucin concentration as a marker of chronic bronchitis","volume":"377","author":"Kesimer","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.4187\/respcare.07521134","article-title":"Physiology of airway mucus secretion and pathophysiology of hypersecretion","volume":"52","author":"Rogers","year":"2007","journal-title":"Respir. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00441-016-2562-z","article-title":"Airway mucus, inflammation and remodeling: Emerging links in the pathogenesis of chronic lung diseases","volume":"367","author":"Duerr","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/07853890600585795","article-title":"Treatment of airway mucus hypersecretion","volume":"38","author":"Rogers","year":"2006","journal-title":"Ann. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.chest.2017.11.008","article-title":"Mucins, mucus, and goblet cells","volume":"154","author":"Ma","year":"2018","journal-title":"Chest"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.molmed.2015.06.003","article-title":"Three cheers for the goblet cell: Maintaining homeostasis in mucosal epithelia","volume":"21","author":"McCauley","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1165\/ajrcmb.25.5.f218","article-title":"Airway mucus obstruction: Mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia","volume":"25","author":"Rose","year":"2001","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1183\/13993003\/erj.9.7.1523","article-title":"The biology of bacterial colonization and invasion of the respiratory mucosa","volume":"9","author":"Wilson","year":"1996","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-micro-091014-104209","article-title":"Mechanisms of bacterial colonization of the respiratory tract","volume":"69","author":"Siegel","year":"2015","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1164\/rccm.200509-1525OC","article-title":"Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease","volume":"173","author":"Sethi","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1183\/09031936.97.10051137","article-title":"Bacterial colonization of distal airways in healthy subjects and chronic lung disease: A bronchoscopic study","volume":"10","author":"Cabello","year":"1997","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bhagirath, A.Y., Li, Y., Somayajula, D., Dadashi, M., Badr, S., and Duan, K. (2016). Cystic fibrosis lung environment and Pseudomonas aeruginosa infection. BMC Pulm. Med., 16.","DOI":"10.1186\/s12890-016-0339-5"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1086\/593186","article-title":"Chronic Pseudomonas aeruginosa infection in chronic obstructive pulmonary disease","volume":"47","author":"Macia","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1183\/09031936.00003309","article-title":"Pseudomonas aeruginosa in patients hospitalised for COPD exacerbation: A prospective study","volume":"34","author":"Almagro","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1128\/AAC.50.1.43-48.2006","article-title":"Multidrug-resistant Pseudomonas aeruginosa: Risk factors and clinical impact","volume":"50","author":"Aloush","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jurado-Mart\u00edn, I., Sainz-Mej\u00edas, M., and McClean, S. (2021). Pseudomonas aeruginosa: An audacious pathogen with an adaptable arsenal of virulence factors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063128"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s13213-011-0273-y","article-title":"Contribution of an arsenal of virulence factors to pathogenesis of Pseudomonas aeruginosa infections","volume":"61","author":"Strateva","year":"2011","journal-title":"Ann. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.molmed.2004.10.002","article-title":"The role of pyocyanin in Pseudomonas aeruginosa infection","volume":"10","author":"Lau","year":"2004","journal-title":"Trends Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1128\/IAI.72.7.4275-4278.2004","article-title":"Pseudomonas aeruginosa pyocyanin is critical for lung infection in mice","volume":"72","author":"Lau","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lew, S.Q., Chong, S.Y., and Lau, G.W. (2025). Modulation of pulmonary immune functions by the Pseudomonas aeruginosa secondary metabolite pyocyanin. Front. Immunol., 16, Erratum in Front Immunol. 2025, 16, 1601361.","DOI":"10.3389\/fimmu.2025.1550724"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6372","DOI":"10.1128\/JB.00505-07","article-title":"Pyocyanin alters redox homeostasis and carbon flux through central metabolic pathways in Pseudomonas aeruginosa PA14","volume":"189","author":"Dietrich","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1111\/j.1365-2958.2006.05306.x","article-title":"The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa","volume":"61","author":"Dietrich","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1465-9921-14-82","article-title":"Pyocyanin-induced mucin production is associated with redox modification of FOXA2","volume":"14","author":"Hao","year":"2013","journal-title":"Respir. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1462-5822.2011.01727.x","article-title":"Pseudomonas aeruginosa pyocyanin causes airway goblet cell hyperplasia and metaplasia and mucus hypersecretion by inactivating the transcriptional factor FoxA2","volume":"14","author":"Hao","year":"2012","journal-title":"Cell. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1172\/JCI112787","article-title":"Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro","volume":"79","author":"Wilson","year":"1987","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1128\/iai.61.7.2848-2853.1993","article-title":"Mechanisms of action of Pseudomonas aeruginosa pyocyanin on human ciliary beat in vitro","volume":"61","author":"Kanthakumar","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/mi.2010.62","article-title":"Reactive oxygen species mediate inflammatory cytokine release and EGFR-dependent mucin secretion in airway epithelial cells exposed to Pseudomonas pyocyanin","volume":"4","author":"Rada","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Xu, Y., Duan, C., Kuang, Z., Hao, Y., Jeffries, J.L., and Lau, G.W. (2013). Pseudomonas aeruginosa pyocyanin activates NRF2-ARE-mediated transcriptional response via the ROS-EGFR-PI3K-AKT\/MEK-ERK MAP kinase signaling in pulmonary epithelial cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072528"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3109\/15419061.2010.551682","article-title":"Interleukin-13 induces mucin 5AC production involving STAT6\/SPDEF in human airway epithelial cells","volume":"17","author":"Yu","year":"2010","journal-title":"Cell Commun. Adhes."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41385-020-0262-1","article-title":"Exendin-4 restores airway mucus homeostasis through the GLP1R-PKA-PPAR\u03b3-FOXA2-phosphatase signaling","volume":"13","author":"Choi","year":"2020","journal-title":"Mucosal Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e12957","DOI":"10.1111\/cmi.12957","article-title":"FOXA2 depletion leads to mucus hypersecretion in canine airways with respiratory diseases","volume":"21","author":"Choi","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ajpath.2020.09.013","article-title":"Pulmonary mycosis drives forkhead box protein A2 degradation and mucus hypersecretion through activation of the spleen tyrosine kinase\u2013epidermal growth factor receptor\u2013AKT\/extracellular signal-regulated kinase 1\/2 signaling","volume":"191","author":"Choi","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1242\/dev.00966","article-title":"Foxa2 regulates alveolarization and goblet cell hyperplasia","volume":"131","author":"Wan","year":"2004","journal-title":"Development"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13809","DOI":"10.1074\/jbc.M414122200","article-title":"Compensatory roles of Foxa1 and Foxa2 during lung morphogenesis","volume":"280","author":"Wan","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"458","DOI":"10.4168\/aair.2015.7.5.458","article-title":"Expression and regulation of transcription factor FoxA2 in chronic rhinosinusitis with and without nasal polyps","volume":"7","author":"Luo","year":"2015","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1038\/s41598-019-39079-4","article-title":"Increase in secreted airway mucins and partial Muc5b STAT6\/FoxA2 regulation during Pneumocystis primary infection","volume":"9","author":"Rojas","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11624","DOI":"10.1073\/pnas.1931483100","article-title":"Insulin regulates the activity of forkhead transcription factor Hnf-3\u03b2\/Foxa-2 by Akt-mediated phosphorylation and nuclear\/cytosolic localization","volume":"100","author":"Wolfrum","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.cmet.2013.01.014","article-title":"Glucagon-induced acetylation of Foxa2 regulates hepatic lipid metabolism","volume":"17","author":"Porstmann","year":"2013","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Van Gent, R., Di Sanza, C., van den Broek, N.J., Fleskens, V., Veenstra, A., Stout, G.J., and Brenkman, A.B. (2014). SIRT1 mediates FOXA2 breakdown by deacetylation in a nutrient-dependent manner. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098438"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"934","DOI":"10.7150\/ijbs.7529","article-title":"SIRT1 deacetylates FOXA2 and is critical for Pdx1 transcription and \u03b2-cell formation","volume":"9","author":"Wang","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/s12974-025-03601-5","article-title":"FOXA2 regulated by HDAC3-mediated deacetylation attenuates neuropathic pain by modulating microglial lipid metabolism and synaptic pruning dysregulation","volume":"22","author":"Zeng","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.3390\/ijms14023834","article-title":"Crosstalk between oxidative stress and SIRT1: Impact on the aging process","volume":"14","author":"Salminen","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1089\/ars.2012.4713","article-title":"SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a\/PGC-1\u03b1 complex","volume":"19","author":"Olmos","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2021.12472","article-title":"Formononetin ameliorates IL-13-induced inflammation and mucus formation in human nasal epithelial cells by activating the SIRT1\/Nrf2 signaling pathway","volume":"24","author":"Huang","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.2353\/ajpath.2009.090166","article-title":"Pseudomonas aeruginosa exotoxin pyocyanin causes cystic fibrosis airway pathogenesis","volume":"175","author":"Caldwell","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"L420","DOI":"10.1152\/ajplung.00316.2002","article-title":"Subcellular localization of Pseudomonas pyocyanin cytotoxicity in human lung epithelial cells","volume":"284","author":"Abdalla","year":"2003","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/nature07813","article-title":"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity","volume":"458","author":"Feige","year":"2009","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3892\/ijmm.2016.2503","article-title":"SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro","volume":"37","author":"Ding","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hori, Y.S., Kuno, A., Hosoda, R., and Horio, Y. (2013). Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073875"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8375","DOI":"10.1074\/jbc.M109.090266","article-title":"Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure","volume":"285","author":"Tanno","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"L94","DOI":"10.1152\/ajplung.00025.2004","article-title":"Pseudomonas aeruginosa pyocyanin directly oxidizes glutathione and decreases its levels in airway epithelial cells","volume":"287","author":"Reszka","year":"2004","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100929","DOI":"10.1016\/j.jbc.2021.100929","article-title":"Resveratrol-induced Sirt1 phosphorylation by LKB1 mediates mitochondrial metabolism","volume":"297","author":"Huang","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"27628","DOI":"10.1074\/jbc.M805711200","article-title":"SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1: Possible role in AMP-activated protein kinase activation","volume":"283","author":"Lan","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature03047","article-title":"Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes","volume":"432","author":"Wolfrum","year":"2004","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.cmet.2005.07.002","article-title":"Foxa2 integrates the transcriptional response of the hepatocyte to fasting","volume":"2","author":"Zhang","year":"2005","journal-title":"Cell Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1172\/JCI21149","article-title":"Foxa2 regulates multiple pathways of insulin secretion","volume":"114","author":"Lantz","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cmet.2006.01.001","article-title":"Coactivation of Foxa2 through Pgc-1\u03b2 promotes liver fatty acid oxidation and triglyceride\/VLDL secretion","volume":"3","author":"Wolfrum","year":"2006","journal-title":"Cell Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24816","DOI":"10.1074\/jbc.M109.042135","article-title":"Nuclear export-independent inhibition of Foxa2 by insulin","volume":"284","author":"Howell","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1172\/JCI60132","article-title":"SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice","volume":"122","author":"Yao","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1164\/rccm.200708-1269OC","article-title":"SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease","volume":"177","author":"Rajendrasozhan","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12272-014-0494-2","article-title":"Role of sirtuins in chronic obstructive pulmonary disease","volume":"38","author":"Chun","year":"2015","journal-title":"Arch. Pharmacal Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1172\/JCI29176","article-title":"SPDEF regulates goblet cell hyperplasia in the airway epithelium","volume":"117","author":"Park","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_68","first-page":"2914","article-title":"SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production","volume":"119","author":"Chen","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Lo Sasso, G., Ryu, D., Mouchiroud, L., Fernando, S.C., Anderson, C.L., Katsyuba, E., Piersigilli, A., Hottiger, M.O., Schoonjans, K., and Auwerx, J. (2014). Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102495"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Wasim, M., Parveen, R., Chen, R., Wang, Y., and Ma, G. (2026). Emerging role of SIRT1 in asthma and COPD from molecular mechanisms to translational therapy. Iscience, 29.","DOI":"10.1016\/j.isci.2026.115909"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Guan, G., Chen, Y., and Dong, Y. (2025). Unraveling the AMPK-SIRT1-FOXO pathway: The in-depth analysis and breakthrough prospects of oxidative stress-induced diseases. Antioxidants, 14.","DOI":"10.3390\/antiox14010070"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1126\/science.1094637","article-title":"Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase","volume":"303","author":"Brunet","year":"2004","journal-title":"science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/mi.2015.119","article-title":"Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewisx to increase binding to airway epithelial cells","volume":"9","author":"Jeffries","year":"2016","journal-title":"Mucosal Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8882\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:12:06Z","timestamp":1791605526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":73,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198882"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198882","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}