{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:46:41Z","timestamp":1790952401823,"version":"4.1.0"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The mucosal barrier, as a critical interface of the body\u2019s defense system, is central to the pathogenesis of allergic diseases, with its structural integrity (epithelial cells, tight junctions, mucus layer, basement membrane) and functional homeostasis being key factors. This paper systematically elucidates the dynamic regulatory network constituted by five major signaling pathways: Wnt\/\u03b2-catenin, TGF-\u03b2\/Smad, RhoA\/ROCK, MAPK, and JAK-STAT. These pathways interact through cross-talk (for example, Smad7 inhibits TGF-\u03b2RI to enhance Wnt signaling, and the \u03b2-catenin\/Smad4 complex synergistically activates EMT genes), forming synergistic\/antagonistic effects that jointly regulate epithelial repair, the expression of tight junction proteins (ZO-1\/Claudin\/Occludin), mucus secretion (MUC2\/MUC5AC), and basement membrane remodeling. In allergic diseases, this network exhibits organ-specific imbalances: respiratory barrier damage is primarily characterized by RhoA\/ROCK-mediated abnormal mucus secretion (asthma) and JAK-STAT-driven Th2 inflammation (rhinitis), whereas the intestinal barrier relies more on the epithelial regenerative capacity of the Wnt pathway.We innovatively propose a \u201cphased-organ-targeting strategy\u201d: during the acute inflammatory phase (0-72 hours), JAK inhibitors (such as CYT387 nasal spray) are utilized to block STAT6 phosphorylation and control the immune storm; in the repair phase (72 hours to 2 weeks), Wnt agonists (WNT2b-pH microspheres) are employed to promote epithelial regeneration, or RhoA regulators (fasudil inhalation) are used to reconstruct the mucus layer; in the chronic remodeling phase, a temporally regulated dual-pathway therapy (such as JAK-STAT inhibition combined with Wnt activation hydrogels) is applied. The current challenges lie in overcoming pathway redundancy, tissue delivery efficiency, and individual differences in microbial flora. Future efforts should focus on achieving precise interventions through local delivery using nanocarriers, temporally coordinated dosing regimens, and predictive models of microbiota-host interactions.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1671677","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:40:37Z","timestamp":1769496037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Research progress on regulatory mechanisms of mucosal barriers and their applications in allergic diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Yipeng","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Tian","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhong","family":"Ning","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12836","DOI":"10.3390\/ijerph182312836","article-title":"Intestinal barrier in human health and disease","volume":"18","author":"Di Tommaso","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B2","doi-asserted-by":"publisher","first-page":"289","DOI":"10.3390\/biomedicines10020289","article-title":"Implication of intestinal barrier dysfunction in gut dysbiosis and diseases","volume":"10","author":"Stolfi","year":"2022","journal-title":"Biomedicines"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0126-x","article-title":"Mechanisms regulating intestinal barrier integrity and its pathological implications","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp Mol Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"89","DOI":"10.22141\/2308-2097.56.2.2022.493","article-title":"Features of the mucous barrier in functional bowel diseases and ulcerative colitis","volume":"56","author":"Dorofeyev","year":"2022","journal-title":"Gastroenterology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0036-x","article-title":"Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier","volume":"16","author":"Martens","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"108002","DOI":"10.1016\/j.exer.2020.108002","article-title":"Corneal epithelial basement membrane: Structure, function and regeneration","volume":"194","author":"Wilson","year":"2020","journal-title":"Exp Eye Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"a029314","DOI":"10.1101\/cshperspect.a029314","article-title":"Cell biology of tight junction barrier regulation and mucosal disease","volume":"10","author":"Buckley","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7821","DOI":"10.3390\/ijms22157821","article-title":"An overview of physical, microbiological and immune barriers of oral mucosa","volume":"22","author":"Senel","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41385-018-0063-y","article-title":"Neuro-immune regulation of mucosal physiology","volume":"12","author":"Chesne","year":"2019","journal-title":"Mucosal Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.663626","article-title":"Nasal epithelial barrier integrity and tight junctions disruption in allergic rhinitis: overview and pathogenic insights","volume":"12","author":"Nur Husna","year":"2021","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1404615","article-title":"Inflammation mechanism and research progress of COPD","volume":"15","author":"Jiao","year":"2024","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S478568","article-title":"Inflammatory and immune mechanisms in COPD: current status and therapeutic prospects","volume":"17","author":"Qi","year":"2024","journal-title":"J. Inflammation Research"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1224129","article-title":"Recent advances in understanding the effects of T lymphocytes on mucosal barrier function in allergic rhinitis","volume":"14","author":"Yang","year":"2023","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nature Reviews Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s00281-024-01026-5","article-title":"The role of the mucosal barrier system in maintaining gut symbiosis to prevent intestinal inflammation","volume":"47","author":"Ryu","year":"2024","journal-title":"Seminars in Immunopathology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41420-024-02015-1","article-title":"Current understanding of the interplay between extracellular matrix remodelling and gut permeability in health and disease","volume":"10","author":"Aurora","year":"2024","journal-title":"Cell Death Discovery"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/\u03b2-catenin signaling, disease, and emerging therapeutic modalities","volume":"169","author":"Roel","year":"2017","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.mucimm.2025.06.004","article-title":"Innate immunity of the gut epithelium: Blowing in the WNT","volume":"18","author":"de Vries","year":"2025","journal-title":"Mucosal Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701086","article-title":"Canonical wnt signaling in CD11c(+) APCs regulates microbiota-induced inflammation and immune cell homeostasis in the colon","volume":"200","author":"Swafford","year":"2018","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.11.082","article-title":"Therapeutic potential of targeting the Wnt\/\u03b2-catenin signaling pathway in colorectal cancer","volume":"110","author":"Xiaofei","year":"2018","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"B21","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.cbi.2018.07.008","article-title":"New insights into TGF-beta\/Smad signaling in tissue fibrosis","volume":"292","author":"Hu","year":"2018","journal-title":"Chem Biol Interact"},{"key":"B22","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ceb.2019.07.007","article-title":"TGF-beta signaling in cell fate control and cancer","volume":"61","author":"Yu","year":"2019","journal-title":"Curr Opin Cell Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.02.090","article-title":"Central role of dysregulation of TGF-beta\/Smad in CKD progression and potential targets of its treatment","volume":"101","author":"Chen","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e31756","DOI":"10.7554\/eLife.31756","article-title":"TGF-beta uses a novel mode of receptor activation to phosphorylate SMAD1\/5 and induce epithelial-to-mesenchymal transition","volume":"7","author":"Ramachandran","year":"2018","journal-title":"Elife"},{"key":"B25","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3390\/cells11010142","article-title":"Structural aspects of LIMK regulation and pharmacology","volume":"11","author":"Deep","year":"2022","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1506356","article-title":"LIM kinases in cardiovascular health and disease","volume":"15","author":"Olubodun","year":"2025","journal-title":"Front Physiology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.03.053","article-title":"Rho GTPases and actomyosin: Partners in regulating epithelial cell-cell junction structure and function","volume":"358","author":"Torey","year":"2017","journal-title":"Exp Cell Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.90624.2007","article-title":"Rho kinases regulate corneal epithelial wound healing","volume":"295","author":"Yin","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"13931","DOI":"10.1038\/s41598-018-32352-y","article-title":"Rotavirus-induced early activation of the rhoA\/ROCK\/MLC signaling pathway mediates the disruption of tight junctions in polarized MDCK cells","volume":"8","author":"Mahmoud","year":"2018","journal-title":"Scientific Reports"},{"key":"B30","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1095\/biolreprod.115.134965","article-title":"The MAPK\/ERK-signaling pathway regulates the expression and distribution of tight junction proteins in the mouse proximal epididymis","volume":"94","author":"Kim","year":"2016","journal-title":"Biol Reprod"},{"key":"B31","doi-asserted-by":"publisher","first-page":"12595","DOI":"10.3390\/ijms222212595","article-title":"Pseudophosphatases as regulators of MAPK signaling","volume":"22","author":"Hepworth","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41540-025-00590-2","article-title":"JNK activation dynamics drive distinct gene expression patterns over time mediated by mRNA stability","volume":"11","author":"Jedariforoughi","year":"2025","journal-title":"npj Systems Biol Appl"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192195","article-title":"The role of IL-22 in intestinal health and disease","volume":"217","author":"Mary","year":"2020","journal-title":"J Exp Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.51362","article-title":"Biological characteristics of IL-6 and related intestinal diseases","volume":"17","author":"Guo","year":"2021","journal-title":"International J. Biological Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00212","article-title":"Targeting cytokine signaling and lymphocyte traffic via small molecules in inflammatory bowel disease: JAK inhibitors and S1PR agonists","volume":"10","author":"Tamara","year":"2019","journal-title":"Front Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"840","DOI":"10.3390\/ph14090840","article-title":"JAK-STAT pathway regulation of intestinal permeability: pathogenic roles and therapeutic opportunities in inflammatory bowel disease","volume":"14","author":"Lei","year":"2021","journal-title":"Pharm (Basel)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2025.01.013","article-title":"Interferon-gamma\/janus kinase 1\/STAT1 signaling represses forkhead box A1 and drives a basal transcriptional state in muscle-invasive bladder cancer","volume":"195","author":"Lawrence","year":"2025","journal-title":"Am J Pathol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"102286","DOI":"10.1016\/j.coi.2023.102286","article-title":"Cytokine-mediated STAT-dependent pathways underpinning human B-cell differentiation and function","volume":"81","author":"Tangye","year":"2023","journal-title":"Curr Opin Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202477099","article-title":"Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation","volume":"99","author":"Seki","year":"2002","journal-title":"Prod Nat Acad Sci USA"},{"key":"B40","doi-asserted-by":"publisher","first-page":"112940","DOI":"10.1016\/j.celrep.2023.112940","article-title":"SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine","volume":"42","author":"Mise-Omata","year":"2023","journal-title":"Cell Reports"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4660","DOI":"10.3390\/molecules27144660","article-title":"Potential natural biomolecules targeting JAK\/STAT\/SOCS signaling in the management of atopic dermatitis","volume":"27","author":"Kopalli","year":"2022","journal-title":"Molecules"},{"key":"B42","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1159\/000528969","article-title":"Epithelial barrier in the nasal mucosa, related risk factors and diseases","volume":"184","author":"Zhang","year":"2023","journal-title":"Int Arch Allergy Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1599355","article-title":"Frizzled receptors: gatekeepers of Wnt signaling in development and disease","volume":"13","author":"Martinez-Marin","year":"2025","journal-title":"Front Cell Dev Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.670960","article-title":"LRP5 and LRP6 in wnt signaling: similarity and divergence","volume":"9","author":"Qian","year":"2021","journal-title":"Front Cell and Development Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.04.021","article-title":"Interplay between microRNAs and WNT\/beta-catenin signalling pathway regulates epithelial-mesenchymal transition in cancer","volume":"51","author":"Ghahhari","year":"2015","journal-title":"Eur J Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2019-213916","article-title":"Effects of Wnt signaling on epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyp","volume":"75","author":"Bae","year":"2020","journal-title":"Thorax"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27718","article-title":"TGFbeta mediates collagen production in human CRSsNP nasal mucosa-derived fibroblasts through Smad2\/3-dependent pathway and CTGF induction and secretion","volume":"234","author":"Shieh","year":"2019","journal-title":"J Cell Physiol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2015.29.4241","article-title":"Differing roles for TGF-\u03b2\/Smad signaling in osteitis in chronic rhinosinusitis with and without nasal polyps","volume":"29","author":"Wang","year":"2015","journal-title":"American Journal of Rhinology & Allergy"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415627681","article-title":"TGF-beta\/SMAD pathway and its regulation in hepatic fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J Histochem Cytochem"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28169","article-title":"Role of TGF-beta signaling regulatory microRNAs in the pathogenesis of colorectal cancer","volume":"234","author":"Soleimani","year":"2019","journal-title":"J Cell Physiol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"3922","DOI":"10.3390\/ijms22083922","article-title":"Involvement of smad7 in inflammatory diseases of the gut and colon cancer","volume":"22","author":"Troncone","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B52","doi-asserted-by":"publisher","first-page":"3550","DOI":"10.3390\/ijms21103550","article-title":"The regulation of intestinal mucosal barrier by myosin light chain kinase\/rho kinases","volume":"21","author":"Jin","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.3390\/jcm9051328","article-title":"ROCK (RhoA\/rho kinase) in cardiovascular-renal pathophysiology: A review of new advancements","volume":"9","author":"Seccia","year":"2020","journal-title":"J Clin Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2018.07.016","article-title":"Effect of simvastatin on the intestinal rho\/ROCK signaling pathway in rats with sepsis","volume":"232","author":"Wang","year":"2018","journal-title":"J Surg Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2020.112","article-title":"Contributions of HO-1-dependent MAPK to regulating intestinal barrier disruption","volume":"29","author":"Zhang","year":"2021","journal-title":"Biomol Ther (Seoul)"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgw005","article-title":"Mucins and Wnt\/beta-catenin signaling in gastrointestinal cancers: an unholy nexus","volume":"37","author":"Pai","year":"2016","journal-title":"Carcinogenesis"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-beta: the master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00260","article-title":"TGF-beta-induced endothelial to mesenchymal transition in disease and tissue engineering","volume":"8","author":"Ma","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"675","DOI":"10.3390\/ijms21020675","article-title":"Cerebral cavernous malformation proteins in barrier maintenance and regulation","volume":"21","author":"Shu","year":"2020","journal-title":"International J Molecular Sciences"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2017.tb00785.x","article-title":"Epithelial organization: the gut and beyond","volume":"7","author":"Nitesh","year":"2017","journal-title":"Comprehensive Physiology"},{"key":"B61","doi-asserted-by":"publisher","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":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s43630-024-00601-x","article-title":"Hypericin-mediated photodynamic therapy inhibits metastasis and EMT of colorectal cancer cells by regulating RhoA-ROCK1 signaling pathway","volume":"23","author":"Jinhang","year":"2024","journal-title":"Photochemical & Photobiological Sciences"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.3390\/ijms20061346","article-title":"Roles of cyclic AMP response element binding activation in the ERK1\/2 and p38 MAPK signalling pathway in central nervous system, cardiovascular system, osteoclast differentiation and mucin and cytokine production","volume":"20","author":"Koga","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.3390\/cells12091224","article-title":"IL-22-activated MUC13 impacts on colonic barrier function through JAK1\/STAT3, SNAI1\/ZEB1 and ROCK2\/MAPK signaling","volume":"12","author":"Breugelmans","year":"2023","journal-title":"Cells"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2018.5827","article-title":"MicroRNA-let-7e regulates the progression and development of allergic rhinitis by targeting suppressor of cytokine signaling 4 and activating Janus kinase 1\/signal transducer and activator of transcription 3 pathway","volume":"15","author":"Li","year":"2018","journal-title":"Exp Ther Med"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1075192","article-title":"Molecular dissection of Janus kinases as drug targets for inflammatory diseases","volume":"13","author":"Kwon","year":"2022","journal-title":"Front Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2017.10.003","article-title":"Overexpression of microRNA-495 improves the intestinal mucosal barrier function by targeting STAT3 via inhibition of the JAK\/STAT3 signaling pathway in a mouse model of ulcerative colitis","volume":"214","author":"Chu","year":"2018","journal-title":"Pathol Res Pract"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2020.06.003","article-title":"HLY78 protects blood-brain barrier integrity through Wnt\/beta-catenin signaling pathway following subarachnoid hemorrhage in rats","volume":"162","author":"Luo","year":"2020","journal-title":"Brain Res Bull"},{"key":"B69","doi-asserted-by":"publisher","first-page":"104774","DOI":"10.1016\/j.phrs.2020.104774","article-title":"MiR-377-3p suppresses colorectal cancer through negative regulation on Wnt\/beta-catenin signaling by targeting XIAP and ZEB2","volume":"156","author":"Huang","year":"2020","journal-title":"Pharmacol Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1042\/bst20200026","article-title":"Extracellular matrix stiffness and Wnt\/\u03b2-catenin signaling in physiology and disease","volume":"48","author":"Pablo","year":"2020","journal-title":"Biochemical Society Transactions"},{"key":"B71","doi-asserted-by":"publisher","first-page":"113307","DOI":"10.1016\/j.biopha.2022.113307","article-title":"Protective effect of oxyberberine against acute lung injury in mice via inhibiting RhoA\/ROCK signaling pathway","volume":"153","author":"Chen","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B72","doi-asserted-by":"publisher","first-page":"12550","DOI":"10.3390\/ijms232012550","article-title":"Zearalenone-induced mechanical damage of intestinal barrier via the rhoA\/ROCK signaling pathway in IPEC-J2 cells","volume":"23","author":"Huang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.617134","article-title":"Cullin3-TNFAIP1 E3 ligase controls inflammatory response in hepatocellular carcinoma cells via ubiquitination of rhoB","volume":"9","author":"Liu","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"8895","DOI":"10.1038\/srep08895","article-title":"P38\/MAPK contributes to endothelial barrier dysfunction via MAP4 phosphorylation-dependent microtubule disassembly in inflammation-induced acute lung injury","volume":"5","author":"Li","year":"2015","journal-title":"Sci Rep"},{"key":"B75","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13046-024-02949-5","article-title":"Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery","volume":"43","author":"Hu","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"B76","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s12944-020-01373-w","article-title":"Ceramide induces MMP-9 expression through JAK2\/STAT3 pathway in airway epithelium","volume":"19","author":"Xuan","year":"2020","journal-title":"Lipids Health Dis"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1101\/2020.06.19.160929","article-title":"Maintaining structural and functional homeostasis of the Drosophila respiratory epithelia requires stress-modulated JAK\/STAT activity","author":"Niu","year":"2022","journal-title":"bioRxiv"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-025-01261-2","article-title":"Type 2 immunity in allergic diseases","volume":"22","author":"Ogulur","year":"2025","journal-title":"Cell Mol Immunol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"546","DOI":"10.3390\/biom14050546","article-title":"The possible roles of IL-4\/IL-13 in the development of eosinophil-predominant severe asthma","volume":"14","author":"Nakagome","year":"2024","journal-title":"Biomolecules"},{"key":"B80","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41392-024-01764-w","article-title":"TGF-\u03b2 signaling in health, disease, and therapeutics","volume":"9","author":"Deng","year":"2024","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"B81","doi-asserted-by":"publisher","first-page":"16492","DOI":"10.1038\/s41598-020-73473-7","article-title":"Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-beta\/Smad2\/3 pathway intensification and antifibrotic TGF-beta\/Smad1\/5\/(8)9 pathway impairment","volume":"10","author":"Wnuk","year":"2020","journal-title":"Sci Rep"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e94801","DOI":"10.1371\/journal.pone.0094801","article-title":"TGF-\u03b2-activated kinase 1 (TAK1) signaling regulates TGF-\u03b2-induced WNT-5A expression in airway smooth muscle cells via Sp1 and \u03b2-catenin","volume":"9","author":"Kuldeep","year":"2014","journal-title":"PLOS ONE"},{"key":"B83","doi-asserted-by":"publisher","first-page":"30676","DOI":"10.1038\/srep30676","article-title":"Regulation of actin dynamics by WNT-5A: implications for human airway smooth muscle contraction","volume":"6","author":"Tim","year":"2016","journal-title":"Scientific Reports"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-05960-1","article-title":"Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells","volume":"66","author":"Ruchi","year":"2023","journal-title":"Diabetologia"},{"key":"B85","doi-asserted-by":"publisher","first-page":"9695","DOI":"10.1038\/s41598-020-66559-9","article-title":"Non-canonical WNT5a regulates Epithelial-to-Mesenchymal Transition in the mouse ovarian surface epithelium","volume":"10","author":"Atefeh","year":"2020","journal-title":"Scientific Reports"},{"key":"B86","doi-asserted-by":"publisher","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":"B87","doi-asserted-by":"publisher","first-page":"357","DOI":"10.3390\/ijms22010357","article-title":"Plasticity of intestinal epithelium: stem cell niches and regulatory signals","volume":"22","author":"Kurokawa","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2024.06.006","article-title":"JAK\/STAT signaling promotes the emergence of unique cell states in ulcerative colitis","volume":"19","author":"Maciag","year":"2024","journal-title":"Stem Cell Rep"},{"key":"B89","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.diff.2019.01.002","article-title":"Wnt signaling in intestinal inflammation","volume":"108","author":"Moparthi","year":"2019","journal-title":"Differentiation"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.238147","article-title":"Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium","volume":"286","author":"Suzuki","year":"2011","journal-title":"J Biol Chem"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkac011","article-title":"Epithelial-mesenchymal transition in organ fibrosis development: current understanding and treatment strategies","volume":"10","author":"Liu","year":"2022","journal-title":"Burns Trauma"},{"key":"B92","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/beta-catenin signalling: function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.3390\/cells13151271","article-title":"The role of transforming growth factor-beta (TGF-beta) in asthma and chronic obstructive pulmonary disease (COPD)","volume":"13","author":"Kraik","year":"2024","journal-title":"Cells"},{"key":"B94","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/s41392-022-01038-3","article-title":"Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy","volume":"7","author":"Pan","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.2147\/JAA.S542695","article-title":"PP2A promotes epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via wnt\/beta-catenin pathway: A novel insight","volume":"18","author":"Chen","year":"2025","journal-title":"J Asthma Allergy"},{"key":"B96","doi-asserted-by":"publisher","first-page":"e33466","DOI":"10.1097\/MD.0000000000033466","article-title":"The function of S100A4 in pulmonary disease: A review","volume":"102","author":"Wang","year":"2023","journal-title":"Med (Baltimore)"},{"key":"B97","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1186\/s12964-024-01957-4","article-title":"The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors","volume":"22","author":"Liaghat","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B98","doi-asserted-by":"publisher","first-page":"e1005400","DOI":"10.1371\/journal.pcbi.1005400","article-title":"The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt","volume":"13","author":"Kay","year":"2017","journal-title":"PloS Comput Biol"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.3390\/ijms21062032","article-title":"Stem cell signaling pathways in the small intestine","volume":"21","author":"Takahashi","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2019.10.005","article-title":"The hippo pathway, YAP\/TAZ, and the plasma membrane","volume":"30","author":"Valentina","year":"2019","journal-title":"Trends in Cell Biology"},{"key":"B101","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.stem.2017.11.001","article-title":"YAP\/TAZ-dependent reprogramming of colonic epithelium links ECM remodeling to tissue regeneration","volume":"22","author":"Yui","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.4161\/tisb.28127","article-title":"The role of angiomotin phosphorylation in the Hippo pathway during preimplantation mouse development","volume":"2","author":"Hirate","year":"2014","journal-title":"Tissue Barriers"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1515364","article-title":"Energy metabolism and the intestinal barrier: implications for understanding and managing intestinal diseases","volume":"16","author":"Chen","year":"2025","journal-title":"Front Microbiol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1120996","article-title":"ROS-AMPK\/mTOR-dependent enterocyte autophagy is involved in the regulation of Giardia infection-related tight junction protein and nitric oxide levels","volume":"14","author":"Wu","year":"2023","journal-title":"Front Immunol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"108943","DOI":"10.1016\/j.cbi.2020.108943","article-title":"Nicotine-induced autophagy via AMPK\/mTOR pathway exerts protective effect in colitis mouse model","volume":"317","author":"Gao","year":"2020","journal-title":"Chem Biol Interact"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.615131","article-title":"Inflammation and wnt signaling: target for immunomodulatory therapy","volume":"8","author":"Jridi","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14508","article-title":"Genetic variants in the TGF\u03b2-signaling pathway influence expression of miRNAs in colon and rectal normal mucosa and tumor tissue","volume":"8","author":"Slattery","year":"2017","journal-title":"Oncotarget"},{"key":"B108","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.imlet.2019.01.007","article-title":"Genetic variants of SMAD2\/3\/4\/7 are associated with susceptibility to ulcerative colitis in a Japanese genetic background","volume":"207","author":"Yamashita","year":"2019","journal-title":"Immunol Lett"},{"key":"B109","doi-asserted-by":"publisher","first-page":"e12860","DOI":"10.1111\/apha.12860","article-title":"Mind the gap: mechanisms regulating the endothelial barrier","volume":"222","author":"Radeva","year":"2018","journal-title":"Acta Physiol (Oxf)"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2019.01.007","article-title":"Role of MKP-5-p38\/MAPK pathway in Clopidogrel-induced gastric mucosal epithelial cells apoptosis and tight junction dysfunction","volume":"12","author":"Hailu","year":"2020","journal-title":"Immunology Letters"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.04.050","article-title":"miR-375 prevents nasal mucosa cells from apoptosis and ameliorates allergic rhinitis via inhibiting JAK2\/STAT3 pathway","volume":"103","author":"Wang","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1068260","article-title":"JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review","volume":"13","author":"Huang","year":"2022","journal-title":"Front Immunol"},{"key":"B113","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1159\/000500637","article-title":"RORA overexpression alleviates nasal mucosal injury and enhances red blood cell immune adhesion function in a mouse model of allergic rhinitis via inactivation of the wnt\/beta-catenin signaling pathway","volume":"180","author":"Li","year":"2019","journal-title":"Int Arch Allergy Immunol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.77","article-title":"Smad3 knockout mice exhibit impaired intestinal mucosal healing","volume":"88","author":"Owen","year":"2008","journal-title":"Lab Invest"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1134","article-title":"RhoA\/Rho-kinases in asthma: from pathogenesis to therapeutic targets","volume":"9","author":"Zhang","year":"2020","journal-title":"Clin Transl Immunol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.9834","article-title":"Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis","volume":"8","author":"Siti Sarah","year":"2020","journal-title":"PeerJ"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.643260","article-title":"Benzo(a)pyrene enhanced dermatophagoides group 1 (Der f 1)-induced TGF\u03b21 signaling activation through the aryl hydrocarbon receptor\u2013rhoA axis in asthma","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-681369\/v1","article-title":"House dust mite induces IL-33 release from human nasal epithelial cells via P2Y purinergic signals and ERK\/P38 MAPK pathways","author":"Liu","year":"2021","journal-title":"Research Square preprint"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2020.619053","article-title":"Xingbi gel ameliorates allergic rhinitis by regulating IFN-gamma gene promoter methylation in CD4+ T cells via the ERK-DNMT pathway","volume":"7","author":"Ai","year":"2020","journal-title":"Front Surg"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-2963-7","article-title":"Inhibition of JAK\/STAT pathway restrains TSLP-activated dendritic cells mediated inflammatory T helper type 2 cell response in allergic rhinitis","volume":"430","author":"Shi","year":"2017","journal-title":"Mol Cell Biochem"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1671677\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:31:51Z","timestamp":1771921911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1671677\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":120,"alternative-id":["10.3389\/fimmu.2026.1671677"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1671677","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"article-number":"1671677"}}