{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:35:59Z","timestamp":1791920159202,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Airway epithelium structure\/function can be altered by local inflammatory\/immune signals, and this process is called epithelial remodeling. The mechanism by which this innate response is regulated, which causes mucin\/mucus overproduction, is largely unknown. Exosomes are nanovesicles that can be secreted and internalized by cells to transport cellular cargo, such as proteins, lipids, and miRNA. The objective of this study was to understand the role exosomes play in airway remodeling through cell\u2013cell communication. We used two different human airway cell cultures: primary human tracheobronchial (HTBE) cells, and a cultured airway epithelial cell line (Calu-3). After intercellular exosomal transfer, comprehensive proteomic and genomic characterization of cell secretions and exosomes was performed. Quantitative proteomics and exosomal miRNA analysis profiles indicated that the two cell types are fundamentally distinct. HTBE cell secretions were typically dominated by fundamental innate\/protective proteins, including mucin MUC5B, and Calu-3 cell secretions were dominated by pathology-associated proteins, including mucin MUC5AC. After exosomal transfer\/intake, approximately 20% of proteins, including MUC5AC and MUC5B, were significantly altered in HTBE secretions. After exosome transfer, approximately 90 miRNAs (\u223c4%) were upregulated in HTBE exosomes, whereas Calu-3 exosomes exhibited a preserved miRNA profile. Together, our data suggest that the transfer of exosomal cargo between airway epithelial cells significantly alters the qualitative and quantitative profiles of airway secretions, including mucin hypersecretion, and the miRNA cargo of exosomes in target cells. This finding indicates that cellular information can be carried between airway epithelial cells via exosomes, which may play an important role in airway biology and epithelial remodeling.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0156oc","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T11:22:05Z","timestamp":1537356125000},"page":"209-220","source":"Crossref","is-referenced-by-count":101,"title":["Intercellular Communication between Airway Epithelial Cells Is Mediated by Exosome-Like Vesicles"],"prefix":"10.1093","volume":"60","author":[{"given":"Richa","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"},{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Radicioni","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"},{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabri","family":"Abdelwahab","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"},{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Dang","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"},{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chua","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr A.","family":"Mieczkowski","sequence":"additional","affiliation":[{"name":"Department of Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"},{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott H.","family":"Randell","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute"},{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Kesimer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"},{"name":"Marsico Lung Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,1]]},"reference":[{"key":"2026012222060073800_bib1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ni.3045","article-title":"Respiratory epithelial cells orchestrate pulmonary innate immunity","volume":"16","author":"Whitsett","year":"2015","journal-title":"Nat Immunol"},{"key":"2026012222060073800_bib2","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1172\/JCI79422","article-title":"Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation","volume":"125","author":"Rajavelu","year":"2015","journal-title":"J Clin Invest"},{"key":"2026012222060073800_bib3","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1038\/mi.2016.27","article-title":"The innate immune properties of airway mucosal surfaces are regulated by dynamic interactions between mucins and interacting proteins: the mucin interactome","volume":"9","author":"Radicioni","year":"2016","journal-title":"Mucosal Immunol"},{"key":"2026012222060073800_bib4","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.coi.2007.08.004","article-title":"Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity","volume":"19","author":"Kato","year":"2007","journal-title":"Curr Opin Immunol"},{"key":"2026012222060073800_bib5","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.bbamem.2007.11.007","article-title":"Interactions of tight junctions with membrane channels and transporters","volume":"1778","author":"Rajasekaran","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"2026012222060073800_bib6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ymeth.2015.03.013","article-title":"Physical characterization and profiling of airway epithelial derived exosomes using light scattering","volume":"87","author":"Kesimer","year":"2015","journal-title":"Methods"},{"key":"2026012222060073800_bib7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1248\/bpb.b12-00607","article-title":"Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing","volume":"36","author":"Ogawa","year":"2013","journal-title":"Biol Pharm Bull"},{"key":"2026012222060073800_bib8","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/gcc.22181","article-title":"Different exosome cargo from plasma\/bronchoalveolar lavage in non\u2013small-cell lung cancer","volume":"53","author":"Rodr\u00edguez","year":"2014","journal-title":"Genes Chromosomes Cancer"},{"key":"2026012222060073800_bib9","doi-asserted-by":"crossref","first-page":"37043","DOI":"10.18632\/oncotarget.6158","article-title":"Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease","volume":"6","author":"Gui","year":"2015","journal-title":"Oncotarget"},{"key":"2026012222060073800_bib10","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/all.12357","article-title":"Differences in exosome populations in human breast milk in relation to allergic sensitization and lifestyle","volume":"69","author":"Torregrosa Paredes","year":"2014","journal-title":"Allergy"},{"key":"2026012222060073800_bib11","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1096\/fj.08-119131","article-title":"Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense","volume":"23","author":"Kesimer","year":"2009","journal-title":"FASEB J"},{"key":"2026012222060073800_bib12","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1172\/JCI87316","article-title":"Extracellular vesicles: masters of intercellular communication and potential clinical interventions","volume":"126","author":"Pitt","year":"2016","journal-title":"J Clin Invest"},{"key":"2026012222060073800_bib13","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat Cell Biol"},{"key":"2026012222060073800_bib14","doi-asserted-by":"crossref","first-page":"842849","DOI":"10.1155\/2011\/842849","article-title":"The roles of tumor-derived exosomes in cancer pathogenesis","volume":"2011","author":"Yang","year":"2011","journal-title":"Clin Dev Immunol"},{"key":"2026012222060073800_bib15","doi-asserted-by":"crossref","first-page":"e0150154","DOI":"10.1371\/journal.pone.0150154","article-title":"Urinary exosomal miRNA signature in type II diabetic nephropathy patients","volume":"11","author":"Deli\u0107","year":"2016","journal-title":"PLoS One"},{"key":"2026012222060073800_bib16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4137\/BMI.S26229","article-title":"Urine proteome biomarkers in kidney diseases. I. Limits, perspectives, and first focus on normal urine","volume":"11","author":"Santucci","year":"2016","journal-title":"Biomark Insights"},{"key":"2026012222060073800_bib17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1165\/rcmb.2015-0108OC","article-title":"Toll-like receptor 4 engagement mediates prolyl endopeptidase release from airway epithelia via exosomes","volume":"54","author":"Szul","year":"2016","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012222060073800_bib18","first-page":"183","article-title":"Well-differentiated human airway epithelial cell cultures","volume":"107","author":"Fulcher","year":"2005","journal-title":"Methods Mol Med"},{"key":"2026012222060073800_bib19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1113\/jphysiol.2007.139840","article-title":"Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells","volume":"584","author":"Kreda","year":"2007","journal-title":"J Physiol"},{"key":"2026012222060073800_bib20","doi-asserted-by":"crossref","first-page":"e0138988","DOI":"10.1371\/journal.pone.0138988","article-title":"Excess secretion of gel-forming mucins and associated innate defense proteins with defective mucin un-packaging underpin gallbladder mucocele formation in dogs","volume":"10","author":"Kesimer","year":"2015","journal-title":"PLoS One"},{"key":"2026012222060073800_bib21","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2026012222060073800_bib22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/biostatistics\/kxm030","article-title":"Small-sample estimation of negative binomial dispersion, with applications to SAGE data","volume":"9","author":"Robinson","year":"2008","journal-title":"Biostatistics"},{"key":"2026012222060073800_bib23","doi-asserted-by":"crossref","first-page":"e101899","DOI":"10.1371\/journal.pone.0101899","article-title":"miR-141 and miR-200c as markers of overall survival in early stage non\u2013small cell lung cancer adenocarcinoma","volume":"9","author":"Tejero","year":"2014","journal-title":"PLoS One"},{"key":"2026012222060073800_bib24","first-page":"64","article-title":"Insights into regulation of the miR-17-92 cluster of miRNAs in cancer","volume":"2","author":"Fuziwara","year":"2015","journal-title":"Front Med (Lausanne)"},{"key":"2026012222060073800_bib25","doi-asserted-by":"crossref","first-page":"e2998","DOI":"10.1038\/cddis.2017.357","article-title":"MicroRNA-34\/449 targets IGFBP-3 and attenuates airway remodeling by suppressing Nur77-mediated autophagy","volume":"8","author":"Yin","year":"2017","journal-title":"Cell Death Dis"},{"key":"2026012222060073800_bib26","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/mi.2012.81","article-title":"Molecular organization of the mucins and glycocalyx underlying mucus transport over mucosal surfaces of the airways","volume":"6","author":"Kesimer","year":"2013","journal-title":"Mucosal Immunol"},{"key":"2026012222060073800_bib27","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":"2026012222060073800_bib28","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1038\/modpathol.2013.101","article-title":"Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype","volume":"26","author":"Walsh","year":"2013","journal-title":"Mod Pathol"},{"key":"2026012222060073800_bib29","doi-asserted-by":"crossref","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":"2026012222060073800_bib30","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.biocel.2015.11.006","article-title":"Glycosylated alpha-1-acid glycoprotein 1 as a potential lung cancer serum biomarker","volume":"70","author":"Ayyub","year":"2016","journal-title":"Int J Biochem Cell Biol"},{"key":"2026012222060073800_bib31","doi-asserted-by":"crossref","first-page":"L92","DOI":"10.1152\/ajplung.90388.2008","article-title":"Tracheobronchial air\u2013liquid interface cell culture: a model for innate mucosal defense of the upper airways?","volume":"296","author":"Kesimer","year":"2009","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012222060073800_bib32","doi-asserted-by":"crossref","first-page":"14118","DOI":"10.1038\/ncomms14118","article-title":"Identification of BPIFA1\/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor","volume":"8","author":"Wu","year":"2017","journal-title":"Nat Commun"},{"key":"2026012222060073800_bib33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1165\/rcmb.2011-0421OC","article-title":"AGR2 is induced in asthma and promotes allergen-induced mucin overproduction","volume":"47","author":"Schroeder","year":"2012","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012222060073800_bib34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4103\/2045-8932.114758","article-title":"Role of microRNAs in lung development and pulmonary diseases","volume":"3","author":"Sessa","year":"2013","journal-title":"Pulm Circ"},{"key":"2026012222060073800_bib35","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrc3318","article-title":"MicroRNAs in the p53 network: micromanagement of tumour suppression","volume":"12","author":"Hermeking","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"2026012222060073800_bib36","doi-asserted-by":"crossref","first-page":"33042","DOI":"10.1038\/srep33042","article-title":"MiR 3180-5p promotes proliferation in human bladder smooth muscle cell by targeting PODN under hydrodynamic pressure","volume":"6","author":"Sun","year":"2016","journal-title":"Sci Rep"},{"key":"2026012222060073800_bib37","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/labinvest.2015.76","article-title":"MicroRNA-19 triggers epithelial-mesenchymal transition of lung cancer cells accompanied by growth inhibition","volume":"95","author":"Li","year":"2015","journal-title":"Lab Invest"},{"key":"2026012222060073800_bib38","doi-asserted-by":"crossref","first-page":"E2851","DOI":"10.1073\/pnas.1407777111","article-title":"Two miRNA clusters, miR-34b\/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis","volume":"111","author":"Wu","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026012222060073800_bib39","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature13413","article-title":"miR-34\/449 miRNAs are required for motile ciliogenesis by repressing cp110","volume":"510","author":"Song","year":"2014","journal-title":"Nature"},{"key":"2026012222060073800_bib40","doi-asserted-by":"crossref","first-page":"pii: eaah5360","DOI":"10.1126\/scitranslmed.aah5360","article-title":"Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice","volume":"9","author":"Neudecker","year":"2017","journal-title":"Sci Transl Med"},{"key":"2026012222060073800_bib41","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1165\/rcmb.2010-0323OC","article-title":"miR-29 is a major regulator of genes associated with pulmonary fibrosis","volume":"45","author":"Cushing","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012222060073800_bib42","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12967-016-0811-2","article-title":"Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma","volume":"14","author":"Felicetti","year":"2016","journal-title":"J Transl Med"},{"key":"2026012222060073800_bib43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","author":"Hoshino","year":"2015","journal-title":"Nature"},{"key":"2026012222060073800_bib44","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.jaci.2013.01.021","article-title":"The exosome in lung diseases: message in a bottle","volume":"131","author":"Eissa","year":"2013","journal-title":"J Allergy Clin Immunol"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/60\/2\/209\/66464831\/ajrcmb_60_2_209.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/60\/2\/209\/66464831\/ajrcmb_60_2_209.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T03:09:00Z","timestamp":1769137740000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/60\/2\/209\/8430324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,1]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2,1]]},"published-print":{"date-parts":[[2019,2,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2018-0156oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,2]]},"published":{"date-parts":[[2019,2,1]]}}}