Gap Junction Protein Connexin43 Exacerbates Lung Vascular Permeability

摘要: Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity mortality associated with Acute Respiratory Distress Syndrome sepsis. Although components of intercellular adhesive tight junctions are critical for maintaining the endothelial barrier, there has been limited study roles gap their component proteins (connexins). Since connexins can modulate inflammatory signaling in other systems, we hypothesized may also regulate permeability. The relationships between response stimuli were studied cultured human cells. Prolonged treatment thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels mRNA protein major connexin, connexin43 (Cx43). Thrombin lipopolysaccharide both communication assayed by transfer microinjected Lucifer yellow. thrombin decreased transendothelial resistance these cells, was attenuated pretreatment connexin inhibitor carbenoxolone. Additionally, decreases produced either reducing Cx43 expression siRNA knockdown. Both carbenoxolone knockdown abrogated thrombin-induced phosphorylation myosin light chain. Taken together, data suggest lung induced conditions be amplified via among