{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T13:03:29Z","timestamp":1789218209225,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OD026582 1R01HL152101 R25GM115298"],"award-info":[{"award-number":["OD026582 1R01HL152101 R25GM115298"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["REZNIKO20I0 REZNIKO19I0"],"award-info":[{"award-number":["REZNIKO20I0 REZNIKO19I0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Club cells are precursors for mucus-producing goblet cells. Interleukin 1\u03b2 (IL-1B) is an inflammatory mediator with pro-mucin activities that increases the number of mucus-producing goblet cells. IL-1B-mediated mucin production in alveolar adenocarcinoma cells requires activation of the cAMP response element-binding protein (CREB). Whether the pro-mucin activities of IL-1B require club cell CREB is unknown.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We challenged male mice with conditional loss of club cell <jats:italic>Creb1<\/jats:italic> and wild type littermates with intra-airway IL-1B or vehicle. Secondarily, we studied human \u201cclub cell-like\u201d H322 cells.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> IL-1B increased whole lung mRNA of secreted (<jats:italic>Mucin 5ac, Mucin 5b<\/jats:italic>) and tethered (<jats:italic>Mucin 1, Mucin 4<\/jats:italic>) mucins independent of genotype. However, loss of club cell Creb1 increased whole lung mRNA of <jats:italic>member RAS oncogene family (Rab3D)<\/jats:italic>, decreased mRNA of the <jats:italic>muscarinic receptor 3 (M3R)<\/jats:italic> and prevented IL-1B mediated increases in <jats:italic>purinergic receptor P2Y, (P2ry2)<\/jats:italic> mRNA. IL-1B increased the density of goblet cells containing neutral mucins in wildtype mice but not in mice with loss of club cell Creb1. These findings suggested that club cell Creb1 regulated mucin secretion. Loss of club cell Creb1 also prevented IL-1B-mediated impairments in airway mechanics. Four days of pharmacologic CREB inhibition in H322 cells increased mRNA abundance of <jats:italic>forkhead box A2 (FOXA2)<\/jats:italic>, a repressor of goblet cell expansion, and decreased mRNA expression of <jats:italic>SAM pointed domain containing ETS transcription factor (SPDEF)<\/jats:italic>, a driver of goblet cell expansion. Chromatin immunoprecipitation demonstrated that CREB directly bound to the promoter region of <jats:italic>FOXA2<\/jats:italic>, but not to the promoter region of <jats:italic>SPDEF<\/jats:italic>. Treatment of H322 cells with IL-1B increased cAMP levels, providing a direct link between IL-1B and CREB signaling.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our findings suggest that club cell Creb1 regulates the pro-mucin properties of IL-1B through pathways likely involving FOXA2.<\/jats:p>","DOI":"10.3389\/fphys.2023.1323865","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T07:57:52Z","timestamp":1703059072000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Club cell CREB regulates the goblet cell transcriptional network and pro-mucin effects of IL-1B"],"prefix":"10.3389","volume":"14","author":[{"given":"Mariana","family":"Sponchiado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina L.","family":"Bonilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz","family":"Mata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalene","family":"Jasso-Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Shin J.","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Fagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Moncada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah R.","family":"Reznikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1164\/rccm.201706-1139OC","article-title":"Mucin production and hydration responses to mucopurulent materials in normal versus cystic fibrosis airway epithelia","volume":"197","author":"Abdullah","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1003470","DOI":"10.1371\/journal.pcbi.1003470","article-title":"The structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer","volume":"10","author":"Acuner Ozbabacan","year":"2014","journal-title":"PLoS Comput. Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1164\/rccm.201307-1268OC","article-title":"Air trapping and airflow obstruction in newborn cystic fibrosis piglets","volume":"188","author":"Adam","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fendo.2013.00129","article-title":"Regulated mucin secretion from airway epithelial cells","volume":"4","author":"Adler","year":"2013","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"19575","DOI":"10.1074\/jbc.M611841200","article-title":"MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines","volume":"282","author":"Baroukh","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1111\/imcb.12459","article-title":"Interleukin-1\u03b2 exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection","volume":"99","author":"Bawazeer","year":"2021","journal-title":"Immunol. Cell Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1164\/ajrccm.159.5.9806044","article-title":"Number and proliferation of clara cells in normal human airway epithelium","volume":"159","author":"Boers","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1165\/rcmb.2006-0116OC","article-title":"IL-1beta disrupts postnatal lung morphogenesis in the mouse","volume":"36","author":"Bry","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e89780","DOI":"10.1172\/jci.insight.89780","article-title":"A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity","volume":"2","author":"Carmona-Rivera","year":"2017","journal-title":"JCI Insight"},{"key":"B10","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/j.1749-6632.2000.tb05529.x","article-title":"Physiological regulation of uteroglobin\/CCSP expression","volume":"923","author":"Chang","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2914","DOI":"10.1172\/JCI39731","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. Invest."},{"key":"B12","doi-asserted-by":"publisher","first-page":"4433","DOI":"10.1172\/JCI125669","article-title":"IL-1\u03b2 dominates the promucin secretory cytokine profile in cystic fibrosis","volume":"129","author":"Chen","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B13","doi-asserted-by":"publisher","first-page":"6133","DOI":"10.4049\/jimmunol.1000223","article-title":"Foxa2 programs Th2 cell-mediated innate immunity in the developing lung","volume":"184","author":"Chen","year":"2010","journal-title":"J. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"L797","DOI":"10.1152\/ajplung.00347.2013","article-title":"IL-1\u03b2 induction of MUC5AC gene expression is mediated by CREB and NF-\u03baB and repressed by dexamethasone","volume":"306","author":"Chen","year":"2014","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"515","DOI":"10.3389\/fimmu.2020.00515","article-title":"Inactivation of FOXA2 by respiratory bacterial pathogens and dysregulation of pulmonary mucus homeostasis","volume":"11","author":"Choi","year":"2020","journal-title":"Front. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"34199","DOI":"10.1074\/jbc.M111.247684","article-title":"The extracellular signal-regulated kinase mitogen-activated protein kinase\/ribosomal S6 protein kinase 1 cascade phosphorylates cAMP response element-binding protein to induce MUC5B gene expression via D-prostanoid receptor signaling","volume":"286","author":"Choi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"23451","DOI":"10.1074\/jbc.M502242200","article-title":"Interleukin-1beta differentially regulates beta2 adrenoreceptor and prostaglandin E2-mediated cAMP accumulation and chloride efflux from Calu-3 bronchial epithelial cells. Role of receptor changes, adenylyl cyclase, cyclo-oxygenase 2, and protein kinase A","volume":"280","author":"Clayton","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.neuron.2011.06.007","article-title":"A role for repressive histone methylation in cocaine-induced vulnerability to stress","volume":"71","author":"Covington","year":"2011","journal-title":"Neuron"},{"key":"B19","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.jcf.2016.05.002","article-title":"Early pulmonary disease manifestations in cystic fibrosis mice","volume":"15","author":"Darrah","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"B20","doi-asserted-by":"publisher","first-page":"eaav3488","DOI":"10.1126\/scitranslmed.aav3488","article-title":"Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis","volume":"11","author":"Esther","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"6281","DOI":"10.1038\/ncomms7281","article-title":"The polymeric mucin Muc5ac is required for allergic airway hyperreactivity","volume":"6","author":"Evans","year":"2015","journal-title":"Nat. Commun."},{"key":"B22","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1165\/rcmb.2004-0060OC","article-title":"Mucin is produced by clara cells in the proximal airways of antigen-challenged mice","volume":"31","author":"Evans","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.jaci.2017.09.035","article-title":"Sputum cell IL-1 receptor expression level is a marker of airway neutrophilia and airflow obstruction in asthmatic patients","volume":"142","author":"Evans","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1186\/1471-2164-14-337","article-title":"Integrative genomic analysis of CREB defines a critical role for transcription factor networks in mediating the fed\/fasted switch in liver","volume":"14","author":"Everett","year":"2013","journal-title":"BMC Genomics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"L671","DOI":"10.1152\/ajplung.00220.2002","article-title":"Neutrophil elastase increases MUC4 expression in normal human bronchial epithelial cells","volume":"284","author":"Fischer","year":"2003","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1165\/rcmb.2009-0313OC","article-title":"NF-\u03baB mediates IL-1\u03b2- and IL-17A-induced MUC5B expression in airway epithelial cells","volume":"45","author":"Fujisawa","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1124\/mol.66.2.337","article-title":"Interleukin-1beta-induced mucin production in human airway epithelium is mediated by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A signaling","volume":"66","author":"Gray","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1183\/09031936.00141514","article-title":"The innate immune function of airway epithelial cells in inflammatory lung disease","volume":"45","author":"Hiemstra","year":"2015","journal-title":"Eur. Respir. J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"25697","DOI":"10.1073\/pnas.1911071116","article-title":"WNT\/RYK signaling restricts goblet cell differentiation during lung development and repair","volume":"116","author":"Kim","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1172\/JCI12568","article-title":"Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis","volume":"107","author":"Kolb","year":"2001","journal-title":"J. Clin. Invest."},{"key":"B31","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.isci.2019.08.011","article-title":"Attenuated amiloride-sensitive current and augmented calcium-activated chloride current in marsh rice rat (Oryzomys palustris) airways","volume":"19","author":"Kuan","year":"2019","journal-title":"iScience"},{"key":"B32","first-page":"3757","article-title":"Metabolism of arachidonic acid in human lung cancer cell lines","volume":"47","author":"Lau","year":"1987","journal-title":"Cancer Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.jcf.2016.01.003","article-title":"Reversible airway obstruction in cystic fibrosis: common, but not associated with characteristics of asthma","volume":"15","author":"Levine","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"B34","doi-asserted-by":"publisher","first-page":"34513","DOI":"10.1038\/srep34513","article-title":"Systemic inhibition of CREB is well-tolerated in vivo","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1177\/154405910308201107","article-title":"Pro-inflammatory cytokines up-regulate MUC1 gene expression in oral epithelial cells","volume":"82","author":"Li","year":"2003","journal-title":"J. Dent. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"L181","DOI":"10.1152\/ajplung.2001.280.1.L181","article-title":"Muc1 mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa","volume":"280","author":"Lillehoj","year":"2001","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"methods"},{"key":"B38","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nm1028","article-title":"Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice","volume":"10","author":"Mall","year":"2004","journal-title":"Nat. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1471-2466-11-33","article-title":"Static and dynamic mechanics of the murine lung after intratracheal bleomycin","volume":"11","author":"Manali","year":"2011","journal-title":"BMC Pulm. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1146\/annurev-med-042921-123443","article-title":"Club cell secretory protein in lung disease: emerging concepts and potential therapeutics","volume":"74","author":"Martinu","year":"2023","journal-title":"Annu. Rev. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/35085068","article-title":"Transcriptional regulation by the phosphorylation-dependent factor CREB","volume":"2","author":"Mayr","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1124\/mol.107.040519","article-title":"Mitogenic effects of cytokines on smooth muscle are critically dependent on protein kinase A and are unmasked by steroids and cyclooxygenase inhibitors","volume":"73","author":"Misior","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"5524","DOI":"10.1210\/jc.2002-020575","article-title":"Interleukin-1beta induces phosphodiesterase 4B2 expression in human myometrial cells through a prostaglandin E2-and cyclic adenosine 3',5'-monophosphate-dependent pathway","volume":"87","author":"Oger","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3044","DOI":"10.1172\/JCI119859","article-title":"Overexpression of Rab3D enhances regulated amylase secretion from pancreatic acini of transgenic mice","volume":"100","author":"Ohnishi","year":"1997","journal-title":"J. Clin. Invest."},{"key":"B45","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1164\/rccm.201804-0734OC","article-title":"Localization of secretory mucins MUC5AC and MUC5B in normal\/healthy human airways","volume":"199","author":"Okuda","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2923","DOI":"10.1038\/s41467-021-23277-8","article-title":"Club cell-specific role of programmed cell death 5 in pulmonary fibrosis","volume":"12","author":"Park","year":"2021","journal-title":"Nat. Commun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nature11130","article-title":"Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung","volume":"487","author":"Pezzulo","year":"2012","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1172\/JCI123524","article-title":"HSP90 inhibitor geldanamycin reverts IL-13- and IL-17-induced airway goblet cell metaplasia","volume":"129","author":"Pezzulo","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B49","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.stem.2009.04.002","article-title":"The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium","volume":"4","author":"Rawlins","year":"2009","journal-title":"Cell Stem Cell"},{"key":"B50","doi-asserted-by":"publisher","first-page":"L133","DOI":"10.1152\/ajplung.00557.2017","article-title":"The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity","volume":"315","author":"Reznikov","year":"2018","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/s0034-5687(00)00209-7","article-title":"Motor control of airway goblet cells and glands","volume":"125","author":"Rogers","year":"2001","journal-title":"Respir. Physiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41525-021-00237-1","article-title":"Smoking shifts human small airway epithelium club cells toward a lesser differentiated population","volume":"6","author":"Rostami","year":"2021","journal-title":"NPJ Genom Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"baw100","DOI":"10.1093\/database\/baw100","article-title":"The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins","volume":"2016","author":"Rouillard","year":"2016","journal-title":"Database (Oxford)"},{"key":"B54","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nature12807","article-title":"Muc5b is required for airway defence","volume":"505","author":"Roy","year":"2014","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1093\/carcin\/12.12.2301","article-title":"Antiproliferative effects of the Ca2+\/calmodulin antagonist B859-35 and the Ca(2+)-channel blocker verapamil on human lung cancer cell lines","volume":"12","author":"Schuller","year":"1991","journal-title":"Carcinogenesis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1210\/mend.13.7.0293","article-title":"A dominant role for the Raf-MEK pathway in forskolin, 12-O-tetradecanoyl-phorbol acetate, and platelet-derived growth factor-induced CREB (cAMP-responsive element-binding protein) activation, uncoupled from serine 133 phosphorylation in NIH 3T3 cells","volume":"13","author":"Seternes","year":"1999","journal-title":"Mol. Endocrinol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1146\/annurev.biochem.68.1.821","article-title":"CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals","volume":"68","author":"Shaywitz","year":"1999","journal-title":"Annu. Rev. Biochem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"23243","DOI":"10.1074\/jbc.M300096200","article-title":"Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK\/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells","volume":"278","author":"Song","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1016\/j.celrep.2018.04.088","article-title":"Regulation of pathogenic T helper 17 cell differentiation by steroid receptor coactivator-3","volume":"23","author":"Tanaka","year":"2018","journal-title":"Cell Rep."},{"key":"B60","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/s0896-6273(00)81010-7","article-title":"Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism","volume":"20","author":"Tao","year":"1998","journal-title":"Neuron"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.4049\/jimmunol.1402123","article-title":"Alternatively spliced myeloid differentiation protein-2 inhibits TLR4-mediated lung inflammation","volume":"194","author":"Tumurkhuu","year":"2015","journal-title":"J. Immunol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"9781","DOI":"10.1074\/jbc.M807849200","article-title":"Synaptotagmin 2 couples mucin granule exocytosis to Ca2+ signaling from endoplasmic reticulum","volume":"284","author":"Tuvim","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B63","doi-asserted-by":"publisher","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":"B64","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1093\/glycob\/cwi061","article-title":"Altered O-glycosylation and sulfation of airway mucins associated with cystic fibrosis","volume":"15","author":"Xia","year":"2005","journal-title":"Glycobiology"},{"key":"B65","doi-asserted-by":"publisher","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":"B66","doi-asserted-by":"publisher","first-page":"4459","DOI":"10.1073\/pnas.0501076102","article-title":"Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues","volume":"102","author":"Zhang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1113\/jphysiol.2007.149310","article-title":"Munc13-2-\/- baseline secretion defect reveals source of oligomeric mucins in mouse airways","volume":"586","author":"Zhu","year":"2008","journal-title":"J. Physiol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1323865\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T07:57:57Z","timestamp":1703059077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1323865\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":67,"alternative-id":["10.3389\/fphys.2023.1323865"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.1323865","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]},"article-number":"1323865"}}