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However, its impact on TJs of ciliated epithelia is sparsely investigated. Herein we elaborated effects of TGF-\u03b21 on TJs of primary human bronchial epithelial cells. We demonstrate that TGF-\u03b21 activates TGF-\u03b21 receptors TGFBR1 and TGFBR2 resulting in ALK5-mediated phosphorylation of SMAD2. We observed that TGFBR1 and -R2 localize specifically on motile cilia. TGF-\u03b21 activated accumulation of phosphorylated SMAD2 (pSMAD2-C) at centrioles of motile cilia and at cell nuclei. This triggered an increase in paracellular permeability via cellular redistribution of claudin 3 (CLDN3) from TJs into cell nuclei followed by disruption of epithelial integrity and formation of epithelial lesions. Only ciliated cells express TGF-\u03b21 receptors; however, nuclear accumulations of pSMAD2-C and CLDN3 redistribution were observed with similar time course in ciliated and non-ciliated cells. In summary, we demonstrate a role of motile cilia in TGF-\u03b21 sensing and showed that TGF-\u03b21 disturbs TJ permeability of conductive airway epithelia by redistributing CLDN3 from TJs into cell nuclei. We conclude that the observed effects contribute to loss of epithelial integrity during atopic asthma.<\/jats:p>","DOI":"10.1007\/s00424-020-02501-2","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T07:03:14Z","timestamp":1609570994000},"page":"287-311","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["TGF-\u03b21 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei"],"prefix":"10.1007","volume":"473","author":[{"given":"Carolin","family":"Schilpp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Lochbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Braubach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Jonigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Frick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Dietl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-6471","authenticated-orcid":false,"given":"Oliver H.","family":"Wittekindt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,2]]},"reference":[{"key":"2501_CR1","doi-asserted-by":"publisher","first-page":"27678","DOI":"10.1074\/jbc.272.44.27678","volume":"272","author":"S Abdollah","year":"1997","unstructured":"Abdollah S, Mac\u00edas-Silva M, Tsukazaki T, Hayashi H, Attisano L, Wrana JL (1997) T\u03b2RI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling. 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