TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei.
Bronchi
/ drug effects
Cells, Cultured
Cilia
/ drug effects
Claudin-3
/ genetics
Electric Impedance
Epithelial Cells
/ drug effects
Humans
Permeability
Phosphorylation
Protein Transport
Receptor, Transforming Growth Factor-beta Type I
/ agonists
Receptor, Transforming Growth Factor-beta Type II
/ agonists
Signal Transduction
Smad2 Protein
/ metabolism
Tight Junctions
/ drug effects
Transforming Growth Factor beta1
/ pharmacology
Claudin 3
Lung
Motile cilia
TGF-β1
Tight junction
Journal
Pflugers Archiv : European journal of physiology
ISSN: 1432-2013
Titre abrégé: Pflugers Arch
Pays: Germany
ID NLM: 0154720
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
13
05
2020
accepted:
03
12
2020
revised:
31
10
2020
pubmed:
3
1
2021
medline:
15
12
2021
entrez:
2
1
2021
Statut:
ppublish
Résumé
TGF-β1 is a major mediator of airway tissue remodelling during atopic asthma and affects tight junctions (TJs) of airway epithelia. However, its impact on TJs of ciliated epithelia is sparsely investigated. Herein we elaborated effects of TGF-β1 on TJs of primary human bronchial epithelial cells. We demonstrate that TGF-β1 activates TGF-β1 receptors TGFBR1 and TGFBR2 resulting in ALK5-mediated phosphorylation of SMAD2. We observed that TGFBR1 and -R2 localize specifically on motile cilia. TGF-β1 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-β1 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-β1 sensing and showed that TGF-β1 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.
Identifiants
pubmed: 33386991
doi: 10.1007/s00424-020-02501-2
pii: 10.1007/s00424-020-02501-2
pmc: PMC7835204
doi:
Substances chimiques
CLDN3 protein, human
0
Claudin-3
0
SMAD2 protein, human
0
Smad2 Protein
0
Transforming Growth Factor beta1
0
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
Receptor, Transforming Growth Factor-beta Type II
EC 2.7.11.30
TGFBR1 protein, human
EC 2.7.11.30
TGFBR2 protein, human
EC 2.7.11.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
287-311Références
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