{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:32Z","timestamp":1792789112418,"version":"4.5.0"},"reference-count":74,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["NIH R01 HL142543"],"award-info":[{"award-number":["NIH R01 HL142543"]}]},{"name":"National Institutes of Health","award":["NIEHS R21 ES038641"],"award-info":[{"award-number":["NIEHS R21 ES038641"]}]},{"name":"University of Kansas Medical Center, School of Medicine, Internal Medicine Start-Up Funds","id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Airway epithelial cells actively regulate allergic asthma through allergen sensing, type 2 cytokine responses, and extracellular vesicle (EV)-mediated intercellular communication. MicroRNAs (miRNAs) are important post-transcriptional regulators of epithelial inflammation and remodeling; however, the extent to which allergen exposure differentially alters cellular and EV-associated miRNA profiles remains incompletely understood. This study characterized miRNA responses to house dust mite (HDM) exposure in BEAS-2B bronchial epithelial cells and their EV-enriched fractions and subsequently examined selected HDM-responsive miRNAs following interleukin-4 (IL-4) stimulation. BEAS-2B cells were exposed to HDM extract or IL-4 for 72 h. EV-enriched preparations were isolated from conditioned media and characterized by transmission electron microscopy, nanoparticle tracking analysis, immunoblotting of EV-associated markers, and uptake assays. Global cellular and EV-associated miRNA profiling was performed in control and HDM-treated samples using the NanoString nCounter Human v3 miRNA assay, followed by qRT-PCR validation of selected candidates. HDM-responsive miRNAs were subsequently evaluated in IL-4-treated cells and corresponding EV-associated RNA by targeted qRT-PCR. Differentially expressed miRNAs were subjected to pathway-enrichment analysis. HDM exposure induced substantial remodeling of the cellular miRNA landscape, with 39 differentially expressed miRNAs identified in BEAS-2B cells. In contrast, EV-associated RNA exhibited a smaller but distinct set of differentially expressed miRNAs, including miR-612, miR-302d-3p, miR-125b-5p, and miR-15a-5p. Notably, miR-15a-5p displayed opposite directional changes in cellular and EV-associated RNA, highlighting compartment-specific differences in miRNA abundance. qRT-PCR independently supported several EV-associated candidates, including miR-612, miR-302d-3p, miR-15a-5p, and miR-125b-5p. Pathway analyses linked HDM-responsive miRNAs to cell-cycle regulation, p53 signaling, FoxO signaling, autophagy, and inflammatory pathways. Targeted qRT-PCR analysis revealed that many selected HDM-responsive miRNAs exhibited reduced expression following IL-4 stimulation compared with their respective untreated controls, indicating different directional responses for several candidates across the two stimulation paradigms . HDM exposure is associated with distinct cellular and EV-associated miRNA responses in the BEAS-2B bronchial epithelial model. The limited overlap between cellular and EV-associated miRNA profiles indicates that specific miRNAs are present at different levels in intracellular and EV compartments. In addition, several HDM-responsive miRNAs exhibited divergent responses following IL-4 stimulation, supporting context-dependent regulation by allergen and cytokine signaling. These findings identify EV-associated miRNAs as candidates for future mechanistic studies in the context of epithelial intercellular communication and allergic airway inflammation.<\/jats:p>","DOI":"10.3390\/cells15191744","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:07:54Z","timestamp":1790240874000},"page":"1744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["House Dust Mite Induces Distinct Cellular and Extracellular Vesicle-Associated miRNA Signatures in BEAS-2B Cells: Targeted Analysis of IL-4 Responses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6742-3460","authenticated-orcid":false,"given":"Isaac Kirubakaran","family":"Sundar","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Giri","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/j.jaci.2020.04.010","article-title":"Epithelial barriers in allergy and asthma","volume":"145","author":"Hellings","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pham, D.D., and Kim, T.B. (2025). Epithelial-derived cytokines in the pathogenesis of severe asthma. Front. Allergy, 6.","DOI":"10.3389\/falgy.2025.1681147"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"230272","DOI":"10.1183\/16000617.0272-2023","article-title":"Harmonising cellular conversations: Decoding the vital roles of extracellular vesicles in respiratory system intercellular communications","volume":"33","author":"Jadamba","year":"2024","journal-title":"Eur. Respir. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/imr.13028","article-title":"Regulation of airway immunity by epithelial miRNAs","volume":"304","author":"Johansson","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Boateng, E., Kovacevic, D., Oldenburg, V., Radinger, M., and Krauss-Etschmann, S. (2022). Role of airway epithelial cell miRNAs in asthma. Front. Allergy, 3.","DOI":"10.3389\/falgy.2022.962693"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"167079","DOI":"10.1016\/j.bbadis.2024.167079","article-title":"House dust mite allergens induce Ca2+ signalling and alarmin responses in asthma airway epithelial cells","volume":"1870","author":"Ouyang","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28649","DOI":"10.1038\/s41598-024-79226-0","article-title":"House dust mites stimulate thymic stromal lymphopoietin production in human bronchial epithelial cells and promote airway remodeling through activation of PAR2 and ERK signaling pathway","volume":"14","author":"Hsieh","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s12016-025-09045-2","article-title":"Targeting IL-13 and IL-4 in Asthma: Therapeutic Implications on Airway Remodeling in Severe Asthma","volume":"68","author":"Sahnoon","year":"2025","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jaci.2022.06.012","article-title":"Modulation of IL-4\/IL-13 cytokine signaling in the context of allergic disease","volume":"150","author":"Shankar","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100309","DOI":"10.1016\/j.impact.2021.100309","article-title":"STAT6-Dependent Exacerbation of House Dust Mite-Induced Allergic Airway Disease in Mice by Multi-Walled Carbon Nanotubes","volume":"22","author":"Ihrie","year":"2021","journal-title":"NanoImpact"},{"key":"ref_11","first-page":"127","article-title":"Recent updates on the role of extracellular vesicles in the pathogenesis of allergic asthma","volume":"2","author":"Srinivasan","year":"2021","journal-title":"Extracell. Vesicles Circ. Nucl. Acids"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mills, J.T., Schwenzer, A., Marsh, E.K., Edwards, M.R., Sabroe, I., Midwood, K.S., and Parker, L.C. (2019). Airway Epithelial Cells Generate Pro-inflammatory Tenascin-C and Small Extracellular Vesicles in Response to TLR3 Stimuli and Rhinovirus Infection. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01987"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.jaci.2021.04.025","article-title":"Epithelial exosomal contactin-1 promotes monocyte-derived dendritic cell-dominant T-cell responses in asthma","volume":"148","author":"Zhang","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Katz-Kiriakos, E., Steinberg, D.F., Kluender, C.E., Osorio, O.A., Newsom-Stewart, C., Baronia, A., Byers, D.E., Holtzman, M.J., Katafiasz, D., and Bailey, K.L. (2021). Epithelial IL-33 appropriates exosome trafficking for secretion in chronic airway disease. JCI Insight, 6.","DOI":"10.1172\/jci.insight.136166"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/all.14008","article-title":"Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development","volume":"75","author":"Bartel","year":"2020","journal-title":"Allergy"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"He, K., Yang, T., Yu, J., Zang, X., Jiang, S., Xu, S., Liu, J., Xu, Z., Wang, W., and Hong, S. (2023). Dermatophagoides farinae microRNAs released to external environments via exosomes regulate inflammation-related gene expression in human bronchial epithelial cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1303265"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.jaci.2012.12.1565","article-title":"Proinflammatory role of epithelial cell-derived exosomes in allergic airway inflammation","volume":"131","author":"Kulshreshtha","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/j.1398-9995.2012.02835.x","article-title":"Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma","volume":"67","author":"Esser","year":"2012","journal-title":"Allergy"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Browne, W., Hopkins, G., Cochrane, S., James, V., Onion, D., and Fairclough, L.C. (2025). The Role of Epithelial-Derived Extracellular Vesicles in Allergic Sensitisation: A Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125791"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1152\/physrev.00032.2024","article-title":"Extracellular vesicles and the lung: From disease pathogenesis to biomarkers and treatments","volume":"105","author":"Park","year":"2025","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.clinthera.2014.05.006","article-title":"Intercellular Communication by Extracellular Vesicles and Their MicroRNAs in Asthma","volume":"36","author":"Fujita","year":"2014","journal-title":"Clin. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/all.15480","article-title":"Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity","volume":"78","author":"Arias","year":"2023","journal-title":"Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/all.70079","article-title":"Extracellular Vesicle miRNAs as Biomarkers of Asthma Severity","volume":"81","author":"Prasad","year":"2025","journal-title":"Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Francisco-Garcia, A.S., Garrido-Mart\u00edn, E.M., Rupani, H., Lau, L.C.K., Martinez-Nunez, R.T., Howarth, P.H., and Sanchez-Elsner, T. (2019). Small RNA Species and microRNA Profiles are Altered in Severe Asthma Nanovesicles from Broncho Alveolar Lavage and Associate with Impaired Lung Function and Inflammation. Non-Coding RNA, 5.","DOI":"10.3390\/ncrna5040051"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Groot, M., and Lee, H. (2020). Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases. Cells, 9.","DOI":"10.3390\/cells9041044"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102206","DOI":"10.1016\/j.labinv.2024.102206","article-title":"Beyond the Bubble: A Debate on microRNA Sorting Into Extracellular Vesicles","volume":"105","author":"Liu","year":"2025","journal-title":"Lab. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Schindler, V.E.M., Alhamdan, F., Preusser, C., Hintz, L., Alhamwe, B.A., Nist, A., Stiewe, T., von Strandmann, E.P., Potaczek, D.P., and Th\u00f6lken, C. (2022). Side-Directed Release of Differential Extracellular Vesicle-associated microRNA Profiles from Bronchial Epithelial Cells of Healthy and Asthmatic Subjects. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030622"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Welsh, J.A., Goberdhan, D.C.I., O\u2019Driscoll, L., Buzas, E.I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T.A.P., and Erdbrugger, U. (2024). Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J. Extracell. Vesicles, 13.","DOI":"10.1002\/jev2.12451"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3.22.1","DOI":"10.1002\/0471143030.cb0322s30","article-title":"Isolation and characterization of exosomes from cell culture supernatants and biological fluids","volume":"30","author":"Thery","year":"2006","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10649","DOI":"10.1021\/acsomega.9b00966","article-title":"Proteomic Analysis of Plasma-Derived Extracellular Vesicles in Smokers and Patients with Chronic Obstructive Pulmonary Disease","volume":"4","author":"Sundar","year":"2019","journal-title":"ACS Omega"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19671","DOI":"10.3402\/jev.v2i0.19671","article-title":"Extracellular vesicle sizing and enumeration by nanoparticle tracking analysis","volume":"2","author":"Gardiner","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1684816","DOI":"10.1080\/20013078.2019.1684816","article-title":"Small RNA-sequence analysis of plasma-derived extracellular vesicle miRNAs in smokers and patients with chronic obstructive pulmonary disease as circulating biomarkers","volume":"8","author":"Sundar","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sundar, I.K., and Srinivasan, A. (2021). Lung miRNA profiles show a time-of-day response in house dust mite-induced allergic asthma in mice. Clin. Transl. Allergy, 11.","DOI":"10.1002\/clt2.12057"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W154","DOI":"10.1093\/nar\/gkad431","article-title":"DIANA-miRPath v4.0: Expanding target-based miRNA functional analysis in cell-type and tissue contexts","volume":"51","author":"Tastsoglou","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D239","DOI":"10.1093\/nar\/gkx1141","article-title":"DIANA-TarBase v8: A decade-long collection of experimentally supported miRNA-gene interactions","volume":"46","author":"Karagkouni","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"D155","DOI":"10.1093\/nar\/gky1141","article-title":"miRBase: From microRNA sequences to function","volume":"47","author":"Kozomara","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D222","DOI":"10.1093\/nar\/gkab1079","article-title":"miRTarBase update 2022: An informative resource for experimentally validated miRNA-target interactions","volume":"50","author":"Huang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jaci.2020.05.051","article-title":"Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype","volume":"146","author":"Camiolo","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Camiolo, M.J., Zhou, X., Wei, Q., Trejo Bittar, H.E., Kaminski, N., Ray, A., and Wenzel, S.E. (2021). Machine learning implicates the IL-18 signaling axis in severe asthma. JCI Insight, 6.","DOI":"10.1172\/jci.insight.149945"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lv, J., and Xiong, X. (2024). Extracellular Vesicle microRNA: A Promising Biomarker and Therapeutic Target for Respiratory Diseases. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179147"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/s12276-020-0450-9","article-title":"Emerging role of extracellular vesicles in the respiratory system","volume":"52","author":"Holtzman","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wahlund, C.J.E., Eklund, A., Grunewald, J., and Gabrielsson, S. (2017). Pulmonary Extracellular Vesicles as Mediators of Local and Systemic Inflammation. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00039"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"112546","DOI":"10.1016\/j.isci.2025.112546","article-title":"Bronchial smooth muscle extracellular vesicles interfere with bronchial epithelium metabolism and function in asthma","volume":"28","author":"Celle","year":"2025","journal-title":"iScience"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yin, H.M., Zhang, S., Sun, Y.H., Li, S., Ning, Y.Y., Dong, Y.C., Shang, Y., and Bai, C. (2017). MicroRNA-34\/449 targets IGFBP-3 and attenuates airway remodeling by suppressing Nur77-mediated autophagy. Cell Death Dis., 8.","DOI":"10.1038\/cddis.2017.357"},{"key":"ref_45","first-page":"1429-U1333","article-title":"MicroRNA-155 is essential for TH2-mediated allergen-induced eosinophilic inflammation in the lung","volume":"133","author":"Alawieh","year":"2014","journal-title":"J. Allergy Clin. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3904\/kjim.2020.132","article-title":"MicroRNA-21 inhibition attenuates airway inflammation and remodelling by modulating the transforming growth factor beta-Smad7 pathway","volume":"36","author":"Hur","year":"2021","journal-title":"Korean J. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Duecker, R.P., Alemdar, O., Wimmers, A., Gronau, L., Chiocchetti, A.G., Valesky, E.M., Donath, H., Trischler, J., Blumchen, K., and Zielen, S. (2024). MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021356"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liu, J., Xu, Z., Yu, J., Zang, X., Jiang, S., Xu, S., Wang, W., and Hong, S. (2024). MiR-146a-5p engineered hucMSC-derived extracellular vesicles attenuate Dermatophagoides farinae-induced allergic airway epithelial cell inflammation. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1443166"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.jaci.2016.06.035","article-title":"MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation","volume":"139","author":"Johansson","year":"2017","journal-title":"J. Allergy Clin. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12481","DOI":"10.1073\/pnas.0605298103","article-title":"NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses","volume":"103","author":"Taganov","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18704","DOI":"10.1073\/pnas.0905063106","article-title":"Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease","volume":"106","author":"Mattes","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lambert, K.A., Roff, A.N., Panganiban, R.P., Douglas, S., and Ishmael, F.T. (2018). MicroRNA-146a is induced by inflammatory stimuli in airway epithelial cells and augments the anti-inflammatory effects of glucocorticoids. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205434"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13601-019-0301-8","article-title":"Reduced expression of miR-146a in human bronchial epithelial cells alters neutrophil migration","volume":"9","author":"Kivihall","year":"2019","journal-title":"Clin. Transl. Allergy"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1111\/cea.13016","article-title":"Selective release of miRNAs via extracellular vesicles is associated with house-dust mite allergen-induced airway inflammation","volume":"47","author":"Gon","year":"2017","journal-title":"Clin. Exp. Allergy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12931-024-02703-7","article-title":"Upregulated microRNA-125b-5p in patients with asthma-COPD overlap mediates oxidative stress and late apoptosis via targeting IL6R\/TRIAP1 signaling","volume":"25","author":"Chang","year":"2024","journal-title":"Respir. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ejphar.2016.04.044","article-title":"miR-125b inhibits goblet cell differentiation in allergic airway inflammation by targeting SPDEF","volume":"782","author":"Liu","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dong, H.N., Yang, W., Li, W., Zhu, S.M., Zhu, L., Gao, P., and Hao, Y.Q. (2023). New insights into autophagy in inflammatory subtypes of asthma. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1156086"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12964-023-01057-9","article-title":"BMAL1\/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma","volume":"21","author":"Chen","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17532","DOI":"10.18632\/oncotarget.8162","article-title":"FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype","volume":"7","author":"Chung","year":"2016","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Yap, H.M., Israf, D.A., Harith, H.H., Tham, C.L., and Sulaiman, M.R. (2019). Crosstalk Between Signaling Pathways Involved in the Regulation of Airway Smooth Muscle Cell Hyperplasia. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01148"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/mi.2017.84","article-title":"MyD88-dependent dendritic and epithelial cell crosstalk orchestrates immune responses to allergens","volume":"11","author":"Thomas","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/cei.12867","article-title":"General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation","volume":"187","author":"Anas","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1007\/s10753-021-01463-6","article-title":"Atractylon Treatment Attenuates Pulmonary Fibrosis via Regulation of the mmu_circ_0000981\/miR-211-5p\/TGFBR2 Axis in an Ovalbumin-Induced Asthma Mouse Model","volume":"44","author":"Zeng","year":"2021","journal-title":"Inflammation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00424-020-02501-2","article-title":"TGF-\u03b21 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei","volume":"473","author":"Schilpp","year":"2021","journal-title":"Pflug. Arch. Eur. J. Phy"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.redox.2018.06.011","article-title":"TGF-beta\/SMAD4 mediated UCP2 downregulation contributes to Aspergillus protease-induced inflammation in primary bronchial epithelial cells","volume":"18","author":"Kim","year":"2018","journal-title":"Redox Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1186\/s12931-024-03052-1","article-title":"Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway","volume":"25","author":"Rao","year":"2024","journal-title":"Respir. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e167395","DOI":"10.1172\/jci.insight.167395","article-title":"Proline is increased in allergic asthma and promotes airway remodeling","volume":"8","author":"Xu","year":"2023","journal-title":"JCI Insight"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kwak, H.J., Park, D.W., Seo, J.Y., Moon, J.Y., Kim, T.H., Sohn, J.W., Shin, D.H., Yoon, H.J., Park, S.S., and Kim, S.H. (2015). The Wnt\/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthma. Exp. Mol. Med., 47.","DOI":"10.1038\/emm.2015.91"},{"key":"ref_69","first-page":"11132","article-title":"YAP is up-regulated in the bronchial airway smooth muscle of the chronic asthma mouse model","volume":"8","author":"Zhou","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.intimp.2011.05.003","article-title":"The active contribution of Toll-like receptors to allergic airway inflammation","volume":"11","author":"Chen","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jakiela, B., Gorka, K., Gross-Sondej, I., Mikrut, S., Okon, K., Sadowski, P., Andrychiewicz, A., Plutecka, H., Stachura, T., and Bochenek, G. (2025). Type 2 gene expression signature in severe asthma associates with more advanced airway remodeling. Clin. Transl. Allergy, 15.","DOI":"10.1002\/clt2.70060"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12931-015-0207-5","article-title":"TWEAK enhances TGF-beta-induced epithelial-mesenchymal transition in human bronchial epithelial cells","volume":"16","author":"Itoigawa","year":"2015","journal-title":"Respir. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1113\/EP090212","article-title":"ZEB1 recruits BRG1 to regulate airway remodelling epithelial-to-mesenchymal transition in asthma","volume":"107","author":"Wang","year":"2022","journal-title":"Exp. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1096\/fj.201600954r","article-title":"Runx2, a novel regulator for goblet cell differentiation and asthma development","volume":"31","author":"Shi","year":"2017","journal-title":"FASEB J."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1744\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:25:03Z","timestamp":1790396703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":74,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cells15191744"],"URL":"https:\/\/doi.org\/10.3390\/cells15191744","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}