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Differential Focal Adhesion Kinase (FAK) Expression Accounts for the Developmental Regulation of Pulmonary Artery Endothelial Cell(PAEC) Barrier Function
Author(s) -
Ying Lihua,
Barnes Elizabeth,
Alvira Cristina,
Cornfield David
Publication year - 2015
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.29.1_supplement.661.7
Subject(s) - focal adhesion , lipopolysaccharide , evans blue , barrier function , andrology , medicine , neonatal sepsis , lung , immunology , microbiology and biotechnology , signal transduction , biology , sepsis
Objective Deferential FAK expression accounts for the developmental regulation of PAEC Barrier Function Methods Lung injury was induced in 6day old (neonatal) and 8week old (adult) mice by Intraperitoneal injection of lipopolysaccharide (LPS) administration. Evans Blue Dye (EBD) was injected in the retro‐orbital sinus vein 24h after LPS, and optical density (OD) of EBD measured in mouse lungs. Barrier function in vitro was assessed in PAEC from neonatal and adult mice using Electric Cell‐substrate Impedance Sensing (ECIS). Gene expression and cytokine profile were evaluated using microarray analysis. FAK expression and gap junction of VE‐Cadherin immuno‐staining were assessed in PAEC with/without FAKsiRNA. Results IP LPS increases lung permeability more in adult, than in neonates. With LPS, barrier function is more well preserved in neonatal, compared to adult PAEC. With LPS, FAK mRNA and protein expression increases more in neonatal, than in adult, PAEC. VE Cadherin membrane localization persists longer in neonatal, than in adult PAEC after LPS. VE cadherin membrane expression was decreased in the adult after 24h FAKsiRNA PAEC transfection. Pharmacologic FAK inhibition compromises barrier function more in adult than in neonatal PAEC. With LPS, adult PAEC FAK overexpression improves and depletion worsens barrier function. Conclusions In response to injury, PAEC barrier function is more well preserved in neonatal, compared to adult lungs. Deferential expression FAK may account for superior barrier function in neonatal PAEC and, perhaps, the survival advantage for children with ARDS. This observation may have important implications for novel cell‐based therapies in adults with ARDS.