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Integrin b1 acetylation-induced transcriptomic reprograming of mouse embryonic endothelial cells and functions

ABSTRACT: Reciprocal regulation of integrin-dependent cell-matrix adhesions and cell-cell junctions is critical for controlling endothelial permeability and proliferation in cancer and inflammatory diseases, but remain poorly understood. Here, we investigated how acetylation of the distal NPKY-motif of b1-integrin influences endothelial cell physiology and barrier function. Expression of an acetylation-mimetic B1A-K794Q-GFP mutant induced transcriptomic reprograming of embryonic endothelial cells particularly in genes responsible for cell adhesion, proliferation, polarity and barrier function. B1A-K794Q-GFP induced a constitutive activation of MAPK signaling, an impairment of junctions, increased proliferation and an altered contact inhibition at confluency. Structural analysis of integrin b1 interaction with KINDLIN-2, biochemical pulldown assay and molecular dynamic analysis showed that acetylation of K794 increases KINDLIN-2 binding to the integrin b1 cytoplasmic tail. Accordingly, altering KINDLIN-2 levels modified Claudin-5 expression and endothelial barrier function. Revealing how integrin b1 acetylation regulates endothelial cell junctions offers new therapeutic possibilities for controlling vascular permeability.

ORGANISM(S): Mus musculus

PROVIDER: GSE238019 | GEO | 2024/01/01

REPOSITORIES: GEO

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