Journal
FEBS LETTERS
Volume 590, Issue 20, Pages 3660-3668Publisher
WILEY-BLACKWELL
DOI: 10.1002/1873-3468.12417
Keywords
claudin-5; FoxO; occludin; permeability; tight junction; ubiquitin
Funding
- Fondation pour la Recherche Medicale
- Institut National du Cancer
- Fondation ARC pour la recherche contre le Cancer
- Ligue Nationale contre le Cancer comite Pays-de-la-Loire
- comite Maine et Loire
- comite Sarthe
- Connect Talent grant from Region Pays-de-la-Loire and Nantes Metropole
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Cell-cell contacts coordinate the endothelial barrier function in response to external cues. To identify new mediators involved in cytokine-promoted endothelial permeability, we screened a siRNA library targeting E3 ubiquitin ligases. Here, we report that silencing of the late endosome/lysosomal membrane-associated RING-CH-3 (MARCH3) enzyme protects the endothelial barrier. Furthermore, transcriptome analysis unmasked the upregulation of the tight junction-encoding gene occludin (OCLN) in MARCH3-depleted cells. Indeed, MARCH3 silencing results in the strengthening of cell-cell contacts, as evidenced by the accumulation of junctional proteins. From a molecular standpoint, the FoxO1 forkhead transcription repressor was inactivated in the absence of MARCH3. This provides a possible molecular link between MARCH3 and the signaling pathway involved in regulating the expression of junctional proteins and barrier integrity.
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