Cx43 levels guide apicobasal polarity in regenerating airway epithelial cells

Article Article scientifique Article Cx43 levels guide apicobasal polarity in regenerating airway epithelial cells eng 2026-06-12 author Badaoui Mehdi 0000-0001-5139-9304 892916 Département de physiologie cellulaire et métabolisme (PHYME) author Luscher Alexandre 660541 Département de médecine (DEMED) author Ma Mengjie 0009-0003-1950-0144 413368 Département de physiologie cellulaire et métabolisme (PHYME) author Bacchetta Marc 94948 Département de physiologie cellulaire et métabolisme (PHYME) author Van Delden Christian 24088 Département de médecine (DEMED) author Kohler Thilo 0000-0003-4889-9492 23327 Département de médecine (DEMED) author Tabernero Arantxa 0000-0001-6302-6134 author Chanson Marc 0000-0001-8104-2090 32865 Département de physiologie cellulaire et métabolisme (PHYME) 10.1038/s42003-026-10413-7 42286068 2399-3642 https://www.nature.com/articles/s42003-026-10413-7 Apicobasal polarity plays key roles in airway epithelial maturation and regeneration. Once polarized, the airway epithelium functions as a barrier against opportunistic pathogens. Yet, the mechanisms that temporally regulate polarization, a process which is disrupted in cystic fibrosis (CF), remain unclear. Here, we demonstrate the functional importance of connexin 43 (Cx43), a gap junction protein, which is normally repressed during regeneration of the airway epithelium. We show that prolonged post-transcriptional stabilization of Cx43 leads to altered collective cell orientation and compromised CF airway epithelial barrier. We report a bidirectional cooperation between Cx43 hemichannel function and adenosine signaling in disrupting ER-Golgi secretory axis, cytoskeleton dynamic and ectopic apical fibronectin production. Genetic and pharmacological inhibition of Cx43 channels re-established polarity and spatial organization of CF airway epithelial cells. Finally, targeting Cx43 hemichannels with mimetic peptides normalizes the CF-dependent fibronectin ectopic expression and prevents the enhanced <i>Pseudomonas aeruginosa</i> trapping to the CF epithelium. Our findings reveal a mechanism in which temporally controlled Cx43-mediated intercellular communication is crucial for coordinating intrinsic polarity programs and maintaining airway epithelium integrity. Dewey 612 Dewey 616 Dewey 618 Swiss National Science Foundation Inter- and intracellular signaling in cystic fibrosis airway epithelium cell polarisation and differentiation 204167 CH 134 Département de physiologie cellulaire et métabolisme 21C 54 Département de microbiologie et médecine moléculaire 21B 58 Département de pédiatrie, gynécologie et obstétrique 223 false 180 Mucoviscidose et jonctions communicantes 229 375 KOHLER THILO 641 235 Perception du Quorum et gènes de virulence 301 Communications biology 6cdf7d76-43d4-42ea-a187-71946de69282 Article (Accepted version) Public s42003-026-10413-7_reference.pdf 9757257 application/pdf CC BY-4.0 9af73ea36ad193e018f2d8efaadc951b6ec4536348504d1c7438299a06074c92 77e9e23e-c136-492b-97fb-42035d8fba82 Supplemental data Public 42003_2026_10413_MOESM2_ESM.pdf 7351193 application/pdf af4b890c887e5c4264762caf6a72dc9929431ea00fb7507a48b341f807aa2f67 openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Cx43 levels guide apicobasal polarity in regenerating airway epithelial cells	Communications biology			2026	5	4

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