{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:13:33Z","timestamp":1791846813436,"version":"4.3.4"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"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","award":["31972908, 81991500, and 81991502"],"award-info":[{"award-number":["31972908, 81991500, and 81991502"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32030010"],"award-info":[{"award-number":["32030010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7202082"],"award-info":[{"award-number":["7202082"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Oral Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sj\u00f6gren\u2019s syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (<jats:italic>Tric<\/jats:italic>\n            <jats:sup>\n              <jats:italic>CKO<\/jats:italic>\n            <\/jats:sup>) mice, and IFN-\u03b3-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, <jats:italic>Tric<\/jats:italic>\n            <jats:sup>\n              <jats:italic>CKO<\/jats:italic>\n            <\/jats:sup> mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK\/STAT1\/miR-145 axis was identified as mediating the IFN-\u03b3-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.<\/jats:p>","DOI":"10.1038\/s41368-025-00349-9","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:10:54Z","timestamp":1742368254000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Loss of tricellular tight junction tricellulin leads to hyposalivation in Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3728-3687","authenticated-orcid":false,"given":"Xiangdi","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainan","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazeng","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihua","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"349_CR1","doi-asserted-by":"publisher","first-page":"278948","DOI":"10.1155\/2010\/278948","volume":"2010","author":"OJ Baker","year":"2010","unstructured":"Baker, O. J. Tight junctions in salivary epithelium. J. Biomed. Biotechnol. 2010, 278948 (2010).","journal-title":"J. Biomed. Biotechnol."},{"key":"349_CR2","doi-asserted-by":"publisher","first-page":"20071","DOI":"10.1074\/jbc.274.29.20071","volume":"274","author":"T Ma","year":"1999","unstructured":"Ma, T. et al. Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels. J. Biol. Chem. 274, 20071\u201320074 (1999).","journal-title":"J. Biol. Chem."},{"key":"349_CR3","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.tcb.2020.08.004","volume":"30","author":"T Otani","year":"2020","unstructured":"Otani, T. & Furuse, M. Tight junction structure and function revisited. Trends Cell Biol. 30, 805\u2013817 (2020).","journal-title":"Trends Cell Biol."},{"key":"349_CR4","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","volume":"20","author":"A Horowitz","year":"2023","unstructured":"Horowitz, A., Chanez-Paredes, S. D., Haest, X. & Turner, J. R. Paracellular permeability and tight junction regulation in gut health and disease. Nat. Rev. Gastroenterol. Hepatol. 20, 417\u2013432 (2023).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"349_CR5","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1083\/jcb.200510043","volume":"171","author":"J Ikenouchi","year":"2005","unstructured":"Ikenouchi, J. et al. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J. Cell Biol. 171, 939\u2013945 (2005).","journal-title":"J. Cell Biol."},{"key":"349_CR6","doi-asserted-by":"publisher","first-page":"3713","DOI":"10.1091\/mbc.e09-01-0080","volume":"20","author":"SM Krug","year":"2009","unstructured":"Krug, S. M. et al. Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Mol. Biol. Cell 20, 3713\u20133724 (2009).","journal-title":"Mol. Biol. Cell"},{"key":"349_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/nyas.13379","volume":"1397","author":"SM Krug","year":"2017","unstructured":"Krug, S. M. Contribution of the tricellular tight junction to paracellular permeability in leaky and tight epithelia. Ann. N. Y. Acad. Sci. 1397, 219\u2013230 (2017).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"349_CR8","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202009037","volume":"221","author":"Y Cho","year":"2022","unstructured":"Cho, Y. et al. Tricellulin secures the epithelial barrier at tricellular junctions by interacting with actomyosin. J. Cell Biol. 221, e202009037 (2022).","journal-title":"J. Cell Biol."},{"key":"349_CR9","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/mi.2017.52","volume":"11","author":"SM Krug","year":"2018","unstructured":"Krug, S. M. et al. Tricellulin is regulated via interleukin-13-receptor alpha2, affects macromolecule uptake, and is decreased in ulcerative colitis. Mucosal Immunol. 11, 345\u2013356 (2018).","journal-title":"Mucosal Immunol."},{"key":"349_CR10","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1177\/0022034519896749","volume":"99","author":"SN Min","year":"2020","unstructured":"Min, S. N. et al. Tricellulin modulates transport of macromolecules in the salivary gland. J. Dent. Res 99, 302\u2013310 (2020).","journal-title":"J. Dent. Res"},{"key":"349_CR11","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41584-023-00932-6","volume":"19","author":"GE Thorlacius","year":"2023","unstructured":"Thorlacius, G. E., Bj\u00f6rk, A. & Wahren-Herlenius, M. Genetics and epigenetics of primary Sj\u00f6gren syndrome: implications for future therapies. Nat. Rev. Rheumatol. 19, 288\u2013306 (2023).","journal-title":"Nat. Rev. Rheumatol."},{"key":"349_CR12","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1093\/rheumatology\/kez578","volume":"59","author":"P Brito-Zer\u00f3n","year":"2020","unstructured":"Brito-Zer\u00f3n, P. et al. Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sj\u00f6gren\u2019s syndrome. Rheumatology 59, 2350\u20132359 (2020).","journal-title":"Rheumatology"},{"key":"349_CR13","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/annrheumdis-2016-210571","volume":"76","author":"CH Shiboski","year":"2017","unstructured":"Shiboski, C. H. et al. 2016 American College of Rheumatology\/European League Against Rheumatism classification criteria for primary Sj\u00f6gren\u2019s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann. Rheum. Dis. 76, 9\u201316 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"349_CR14","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1073\/pnas.0510837103","volume":"103","author":"JE Gottenberg","year":"2006","unstructured":"Gottenberg, J. E. et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sj\u00f6gren\u2019s syndrome. Proc. Natl Acad. Sci. USA 103, 2770\u20132775 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"349_CR15","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.freeradbiomed.2023.05.027","volume":"205","author":"T Cao","year":"2023","unstructured":"Cao, T. et al. Interferon-\u03b3 induces salivary gland epithelial cell ferroptosis in Sjogren\u2019s syndrome via JAK\/STAT1-mediated inhibition of system Xc. Free Radic. Biol. Med. 205, 116\u2013128 (2023).","journal-title":"Free Radic. Biol. Med."},{"key":"349_CR16","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41584-021-00605-2","volume":"17","author":"GM Verstappen","year":"2021","unstructured":"Verstappen, G. M., Pringle, S., Bootsma, H. & Kroese, F. G. M. Epithelial-immune cell interplay in primary Sj\u00f6gren syndrome salivary gland pathogenesis. Nat. Rev. Rheumatol. 17, 333\u2013348 (2021).","journal-title":"Nat. Rev. Rheumatol."},{"key":"349_CR17","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1136\/annrheumdis-2020-218467","volume":"80","author":"R Felten","year":"2021","unstructured":"Felten, R. et al. Interleukin 6 receptor inhibition in primary Sj\u00f6gren syndrome: a multicentre double-blind randomised placebo-controlled trial. Ann. Rheum. Dis. 80, 329\u2013338 (2021).","journal-title":"Ann. Rheum. Dis."},{"key":"349_CR18","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1136\/annrheumdis-2020-218599","volume":"80","author":"AN Baer","year":"2021","unstructured":"Baer, A. N. et al. Efficacy and safety of abatacept in active primary Sj\u00f6gren\u2019s syndrome: results of a phase III, randomised, placebo-controlled trial. Ann. Rheum. Dis. 80, 339\u2013348 (2021).","journal-title":"Ann. Rheum. Dis."},{"key":"349_CR19","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1093\/rheumatology\/32.7.578","volume":"32","author":"R Jonsson","year":"1993","unstructured":"Jonsson, R., Kroneld, U., B\u00e4ckman, K., Magnusson, B. & Tarkowski, A. Progression of sialadenitis in Sj\u00f6gren\u2019s syndrome. Br. J. Rheumatol. 32, 578\u2013581 (1993).","journal-title":"Br. J. Rheumatol."},{"key":"349_CR20","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1002\/art.30295","volume":"63","author":"AAM Bookman","year":"2011","unstructured":"Bookman, A. A. M. et al. Whole stimulated salivary flow: correlation with the pathology of inflammation and damage in minor salivary gland biopsy specimens from patients with primary Sj\u00f6gren\u2019s syndrome but not patients with sicca. Arthritis Rheum. 63, 2014\u20132020 (2011).","journal-title":"Arthritis Rheum."},{"key":"349_CR21","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1002\/art.27362","volume":"62","author":"P Ewert","year":"2010","unstructured":"Ewert, P. et al. Disruption of tight junction structure in salivary glands from Sj\u00f6gren\u2019s syndrome patients is linked to proinflammatory cytokine exposure. Arthritis Rheum. 62, 1280\u20131289 (2010).","journal-title":"Arthritis Rheum."},{"key":"349_CR22","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1177\/0022034516634647","volume":"95","author":"LW Zhang","year":"2016","unstructured":"Zhang, L. W. et al. Interleukin-17 impairs salivary tight junction integrity in Sjogren\u2019s syndrome. J. Dent. Res. 95, 784\u2013792 (2016).","journal-title":"J. Dent. Res."},{"key":"349_CR23","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.rdc.2016.03.004","volume":"42","author":"S Katsiougiannis","year":"2016","unstructured":"Katsiougiannis, S. & Wong, D. T. W. The proteomics of saliva in Sj\u00f6gren\u2019s syndrome. Rheum. Dis. Clin. North Am. 42, 449\u2013456, (2016).","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"349_CR24","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1177\/1535370216681550","volume":"242","author":"KE Kaczor-Urbanowicz","year":"2017","unstructured":"Kaczor-Urbanowicz, K. E. et al. Saliva diagnostics\u2014current views and directions. Exp. Biol. Med. (Maywood) 242, 459\u2013472 (2017).","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"349_CR25","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.clim.2017.05.001","volume":"182","author":"AB Peck","year":"2017","unstructured":"Peck, A. B. & Nguyen, C. Q. What can Sj\u00f6gren\u2019s syndrome-like disease in mice contribute to human Sj\u00f6gren\u2019s syndrome? Clin. Immunol. 182, 14\u201323 (2017).","journal-title":"Clin. Immunol."},{"key":"349_CR26","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1136\/ard.2006.064030","volume":"66","author":"SD Tran","year":"2007","unstructured":"Tran, S. D. et al. Reversal of Sjogren\u2019s-like syndrome in non-obese diabetic mice. Ann. Rheum. Dis. 66, 812\u2013814 (2007).","journal-title":"Ann. Rheum. Dis."},{"key":"349_CR27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41392-021-00824-9","volume":"7","author":"L Zhang","year":"2022","unstructured":"Zhang, L. et al. Integrated single-cell RNA sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer. Signal Transduct. Target Ther. 7, 9 (2022).","journal-title":"Signal Transduct. Target Ther."},{"key":"349_CR28","doi-asserted-by":"publisher","first-page":"1405126","DOI":"10.3389\/fimmu.2024.1405126","volume":"15","author":"W Qi","year":"2024","unstructured":"Qi, W. et al. Advances in cellular and molecular pathways of salivary gland damage in Sj\u00f6gren\u2019s syndrome. Front. Immunol. 15, 1405126 (2024).","journal-title":"Front. Immunol."},{"key":"349_CR29","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005","volume":"4","author":"V Agarwal","year":"2015","unstructured":"Agarwal, V., Bell, G. W., Nam, J. W. & Bartel, D. P. Predicting effective microRNA target sites in mammalian mRNAs. Elife 4, e05005 (2015).","journal-title":"Elife"},{"key":"349_CR30","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.coph.2009.06.022","volume":"9","author":"KL Edelblum","year":"2009","unstructured":"Edelblum, K. L. & Turner, J. R. The tight junction in inflammatory disease: communication breakdown. Curr. Opin. Pharm. 9, 715\u2013720 (2009).","journal-title":"Curr. Opin. Pharm."},{"key":"349_CR31","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1086\/510022","volume":"79","author":"S Riazuddin","year":"2006","unstructured":"Riazuddin, S. et al. Tricellulin is a tight-junction protein necessary for hearing. Am. J. Hum. Genet. 79, 1040\u20131051 (2006).","journal-title":"Am. J. Hum. Genet."},{"key":"349_CR32","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1242\/jcs.072058","volume":"124","author":"S Masuda","year":"2011","unstructured":"Masuda, S. et al. LSR defines cell corners for tricellular tight junction formation in epithelial cells. J. Cell Sci. 124, 548\u2013555 (2011).","journal-title":"J. Cell Sci."},{"key":"349_CR33","doi-asserted-by":"publisher","first-page":"4687","DOI":"10.1091\/mbc.e08-05-0530","volume":"19","author":"J Ikenouchi","year":"2008","unstructured":"Ikenouchi, J., Sasaki, H., Tsukita, S., Furuse, M. & Tsukita, S. Loss of occludin affects tricellular localization of tricellulin. Mol. Biol. Cell 19, 4687\u20134693 (2008).","journal-title":"Mol. Biol. Cell"},{"key":"349_CR34","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/rai2.12052","volume":"2","author":"VH Letawsky","year":"2022","unstructured":"Letawsky, V. H. et al. Exploring salivary biomarkers and swallowing perceptions in Sjogren\u2019s syndrome: a case-control feasibility study. Rheumatol. Autoimmun. 2, 129\u2013140 (2022).","journal-title":"Rheumatol. Autoimmun."},{"key":"349_CR35","doi-asserted-by":"publisher","first-page":"R194","DOI":"10.1186\/ar3523","volume":"13","author":"C Baldini","year":"2011","unstructured":"Baldini, C. et al. Proteomic analysis of saliva: a unique tool to distinguish primary Sj\u00f6gren\u2019s syndrome from secondary Sj\u00f6gren\u2019s syndrome and other sicca syndromes. Arthritis Res. Ther. 13, R194 (2011).","journal-title":"Arthritis Res. Ther."},{"key":"349_CR36","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jaut.2019.03.008","volume":"100","author":"J Lee","year":"2019","unstructured":"Lee, J. et al. Soluble siglec-5 is a novel salivary biomarker for primary Sjogren\u2019s syndrome. J. Autoimmun. 100, 114\u2013119 (2019).","journal-title":"J. Autoimmun."},{"key":"349_CR37","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1177\/0394632016651273","volume":"29","author":"S Benchabane","year":"2016","unstructured":"Benchabane, S. et al. A case for IL-6, IL-17A, and nitric oxide in the pathophysiology of Sj\u00f6gren\u2019s syndrome. Int. J. Immunopathol. Pharm. 29, 386\u2013397 (2016).","journal-title":"Int. J. Immunopathol. Pharm."},{"key":"349_CR38","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s10067-016-3186-0","volume":"35","author":"K Jayakanthan","year":"2016","unstructured":"Jayakanthan, K. et al. Younger patients with primary Sj\u00f6gren\u2019s syndrome are more likely to have salivary IgG anti-muscarinic acetylcholine receptor type 3 antibodies. Clin. Rheumatol. 35, 657\u2013662 (2016).","journal-title":"Clin. Rheumatol."},{"key":"349_CR39","volume":"13","author":"B Khatri","year":"2022","unstructured":"Khatri, B. et al. Genome-wide association study identifies Sj\u00f6gren\u2019s risk loci with functional implications in immune and glandular cells. Nat. Commun. 13, 598 (2022).","journal-title":"Nat. Commun."},{"key":"349_CR40","doi-asserted-by":"publisher","first-page":"C1191","DOI":"10.1152\/ajpcell.00144.2008","volume":"295","author":"OJ Baker","year":"2008","unstructured":"Baker, O. J. et al. Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line. Am. J. Physiol. Cell Physiol. 295, C1191\u2013C1201 (2008).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"349_CR41","doi-asserted-by":"publisher","first-page":"69","DOI":"10.7150\/ijbs.22259","volume":"14","author":"M Yu","year":"2018","unstructured":"Yu, M. et al. Aryl hydrocarbon receptor activation modulates intestinal epithelial barrier function by maintaining tight junction integrity. Int. J. Biol. Sci. 14, 69\u201377 (2018).","journal-title":"Int. J. Biol. Sci."},{"key":"349_CR42","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.ajpath.2015.12.016","volume":"186","author":"R Al-Sadi","year":"2016","unstructured":"Al-Sadi, R., Guo, S., Ye, D., Rawat, M. & Ma, T. Y. TNF-\u03b1 modulation of intestinal tight junction permeability is mediated by NIK\/IKK-\u03b1 axis activation of the canonical NF-\u03baB pathway. Am. J. Pathol. 186, 1151\u20131165 (2016).","journal-title":"Am. J. Pathol."},{"key":"349_CR43","doi-asserted-by":"publisher","first-page":"e61944","DOI":"10.1371\/journal.pone.0061944","volume":"8","author":"M Cao","year":"2013","unstructured":"Cao, M., Wang, P., Sun, C., He, W. & Wang, F. Amelioration of IFN-\u03b3 and TNF-\u03b1-induced intestinal epithelial barrier dysfunction by berberine via suppression of MLCK-MLC phosphorylation signaling pathway. PloS ONE 8, e61944 (2013).","journal-title":"PloS ONE"},{"key":"349_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00692-w","volume":"19","author":"K Kunimura","year":"2021","unstructured":"Kunimura, K., Miki, S., Takashima, M. & Suzuki, J. I. S-1-propenylcysteine improves TNF-\u03b1-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1\/RhoA\/Rac pathway. Cell Commun. Signal. 19, 17 (2021).","journal-title":"Cell Commun. Signal."},{"key":"349_CR45","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1177\/00220345231210547","volume":"103","author":"L He","year":"2024","unstructured":"He, L. et al. Claudin-10 decrease in the submandibular gland contributes to xerostomia. J. Dent. Res. 103, 167\u2013176 (2024).","journal-title":"J. Dent. Res."},{"key":"349_CR46","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/s41576-023-00611-y","volume":"24","author":"R Shang","year":"2023","unstructured":"Shang, R., Lee, S., Senavirathne, G. & Lai, E. C. MicroRNAs in action: biogenesis, function and regulation. Nat. Rev. Genet. 24, 816\u2013833 (2023).","journal-title":"Nat. Rev. Genet."},{"key":"349_CR47","doi-asserted-by":"publisher","first-page":"767456","DOI":"10.3389\/fimmu.2021.767456","volume":"12","author":"LW Kaminsky","year":"2021","unstructured":"Kaminsky, L. W., Al-Sadi, R. & Ma, T. Y. IL-1\u03b2 and the intestinal epithelial tight junction barrier. Front. Immunol. 12, 767456 (2021).","journal-title":"Front. Immunol."},{"key":"349_CR48","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.3390\/cells10113230","volume":"10","author":"Y Huang","year":"2021","unstructured":"Huang, Y. et al. High glucose reduces the paracellular permeability of the submandibular gland epithelium via the miR-22-3p\/Sp1\/claudin pathway. Cells 10, 3230 (2021).","journal-title":"Cells"},{"key":"349_CR49","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1093\/carcin\/bgac033","volume":"43","author":"CX Hou","year":"2022","unstructured":"Hou, C. X. et al. Exosomal microRNA-23b-3p promotes tumor angiogenesis and metastasis by targeting PTEN in salivary adenoid cystic carcinoma. Carcinogenesis 43, 682\u2013692 (2022).","journal-title":"Carcinogenesis"},{"key":"349_CR50","doi-asserted-by":"publisher","first-page":"685837","DOI":"10.3389\/fimmu.2021.685837","volume":"12","author":"D Jara","year":"2021","unstructured":"Jara, D. et al. Type I interferon dependent hsa-miR-145-5p downregulation modulates MUC1 and TLR4 overexpression in salivary glands from Sj\u00f6gren\u2019s syndrome patients. Front. Immunol. 12, 685837 (2021).","journal-title":"Front. Immunol."},{"key":"349_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15831-7","volume":"11","author":"N Tajik","year":"2020","unstructured":"Tajik, N. et al. Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis. Nat. Commun. 11, 1995 (2020).","journal-title":"Nat. Commun."},{"key":"349_CR52","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1053\/j.gastro.2015.02.008","volume":"148","author":"DA Leffler","year":"2015","unstructured":"Leffler, D. A. et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology 148, 1311\u20139.e6 (2015).","journal-title":"Gastroenterology"},{"key":"349_CR53","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149633","volume":"131","author":"LM Yonker","year":"2021","unstructured":"Yonker, L. M. et al. Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. J. Clin. Invest. 131, e149633 (2021).","journal-title":"J. Clin. Invest."},{"key":"349_CR54","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1177\/0022034519837240","volume":"98","author":"A Limaye","year":"2019","unstructured":"Limaye, A. et al. Targeted TNF-alpha overexpression drives salivary gland inflammation. J. Dent. Res. 98, 713\u2013719 (2019).","journal-title":"J. Dent. Res."},{"key":"349_CR55","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/labinvest.2012.159","volume":"93","author":"O Dubrovskyi","year":"2013","unstructured":"Dubrovskyi, O., Birukova, A. A. & Birukov, K. G. Measurement of local permeability at subcellular level in cell models of agonist- and ventilator-induced lung injury. Lab Invest. 93, 254\u2013263 (2013).","journal-title":"Lab Invest."},{"key":"349_CR56","doi-asserted-by":"crossref","unstructured":"Mao, X., Min, S., He, Q. & Cong, X. In vivo vascular permeability detection in mouse submandibular gland. J. Vis. Exp. 186, e64167 (2022).","DOI":"10.3791\/64167-v"}],"container-title":["International Journal of Oral Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41368-025-00349-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41368-025-00349-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41368-025-00349-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:44:59Z","timestamp":1742370299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41368-025-00349-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["349"],"URL":"https:\/\/doi.org\/10.1038\/s41368-025-00349-9","relation":{},"ISSN":["2049-3169"],"issn-type":[{"value":"2049-3169","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"assertion":[{"value":"26 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22"}}