JAM-A Acts via C/EBP-α to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function.

Circulation Research
Nikolaos KakogiannosMonica Giannotta

Abstract

Intercellular tight junctions are crucial for correct regulation of the endothelial barrier. Their composition and integrity are affected in pathological contexts, such as inflammation and tumor growth. JAM-A (junctional adhesion molecule A) is a transmembrane component of tight junctions with a role in maintenance of endothelial barrier function, although how this is accomplished remains elusive. We aimed to understand the molecular mechanisms through which JAM-A expression regulates tight junction organization to control endothelial permeability, with potential implications under pathological conditions. Genetic deletion of JAM-A in mice significantly increased vascular permeability. This was associated with significantly decreased expression of claudin-5 in the vasculature of various tissues, including brain and lung. We observed that C/EBP-α (CCAAT/enhancer-binding protein-α) can act as a transcription factor to trigger the expression of claudin-5 downstream of JAM-A, to thus enhance vascular barrier function. Accordingly, gain-of-function for C/EBP-α increased claudin-5 expression and decreased endothelial permeability, as measured by the passage of fluorescein isothiocyanate (FITC)-dextran through endothelial monolayers. ...Continue Reading

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Citations

Mar 14, 2021·The American Journal of Pathology·Julianne W Ashby, Julia J Mack
Jun 22, 2021·Tissue Barriers·Anna Agata ScaliseMonica Giannotta

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Methods Mentioned

BETA
GTPase
confocal microscopy
transmission electron microscopy
confocal
immunoprecipitation
transfection
electron microscopy
biopsies

Software Mentioned

FLASH
TOP
Affymetrix
FOP
MYNERVA

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