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Adenosine monophosphate‐activated kinase α1 promotes endothelial barrier repair
Author(s) -
Creighton Judy,
Jian MingYuan,
Sayner Sarah,
Alexeyev Mikhail,
Insel Paul A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-179218
Subject(s) - ampk , microbiology and biotechnology , adherens junction , protein kinase a , endothelial stem cell , barrier function , chemistry , cyclic adenosine monophosphate , cell , biology , kinase , cadherin , biochemistry , in vitro , receptor
The vascular endothelium responds to damage through activation of multiple signaling events that restore cell‐cell adhesion and vascular integrity. However, the molecular mechanisms that integrate these events are not clearly defined. Herein, we identify a previously unexpected role for adenosine monophosphate‐activated protein kinase (AMPK) in pulmonary microvascular endothelial cell (PMVEC) repair. PMVECs selectively express the AMPKα1 catalytic subunit, pharmacological and short hairpin RNA‐mediated inhibition of which attenuates Ca 2+ entry in these cells induced by the inflammatory Ca 2+ ‐signaling mimetic thapsigargin. We find that AMPKα1 activity is required for the formation of PMVEC cell‐cell networks in a prorepair environment and for monolayer resealing after wounding. Decreasing AMPKα1 expression reduces barrier resistance in PMVEC monolayers, results consistent with a role for AMPKα1 in cell‐cell adhesion. AMPKα1 colocalizes and coimmunoprecipitates with the adherens junction protein N‐cadherin and cofractionates with proteins selectively expressed in caveolar membranes. Assessment of permeability, by measuring the filtration coefficient ( K f ) in isolated perfused lungs, confirmed that AMPK activation contributes to barrier repair in vivo. Our findings thus provide novel evidence for AMPKα1 in Ca 2+ influx‐mediated signaling and wound repair in the endothelium.—Creighton, J., Jian, M., Sayner, S., Alexeyev, M., Insel, P. A. Adenosine monophosphate‐activated kinase α1 promotes endothelial barrier repair. FASEB J. 25, 3356–3365 (2011). www.fasebj.org