Premium
N‐cadherin contributes to the pulmonary microvascular endothelial response to LPS
Author(s) -
Jian MingYuan,
Creighton Judy
Publication year - 2013
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/fasebj.27.1_supplement.724.12
Subject(s) - ve cadherin , lipopolysaccharide , cadherin , ampk , microcirculation , chemistry , tight junction , lung , prostacyclin , inflammation , endothelial stem cell , microbiology and biotechnology , medicine , immunology , biology , cell , in vitro , biochemistry , protein kinase a , kinase
Lipopolysaccharide (LPS) is known to damage the lung's microcirculation resulting in loss of endothelial barrier integrity and increased edema. We have shown previously that AMPK activation resolves this injury. In lung pulmonary microvascular cells (PMVECs), AMPKα1 localizes to a discreet membrane compartment with N‐cadherin leading us to hypothesize that N‐cadherin was involved in the PMVEC response to LPS. Inhibition of N‐cadherin using a blocking antibody impaired endothelial formation of a tight pulmonary microvascular barrier and delayed monolayer resealing. This effect was exacerbated in the presence of LPS. Wounded control monolayers resealed at a velocity of 6 μm/sec, whereas LPS reduced the resealing rate to 4 μm/sec. In PMVECs expressing shRNA to N‐cadherin (ΔN‐cad), which reduced N‐cadherin content by 80%, the resealing rate in the presence of LPS was 2 μm/sec. Moreover, the ΔN‐cad cells were 4 fold more sensitive to LPS‐induced injury. These data provide evidence that N‐cadherin and AMPK work in tandem in the PMVEC response to LPS‐induced endothelial injury. Supported by HL102296 and HL 110803.