%0 Journal Article %A Khadija Ourradi %A Thomas Blythe %A Shaney Barratt %A Caroline Jarett %A Gavin Welsh %A Ann Millar %T LSC 2013 abstract - Unravelling VEGF165 signalling in the lung %D 2013 %J European Respiratory Journal %P P4883 %V 42 %N Suppl 57 %X Vascular endothelial growth factor (VEGF) is a potent mitogenic, angiogenic and permeability factor implicated in both the development of lung injury and repair in several respiratory diseases such as ARDS and IPF. VEGF165 acts through VEGF receptors in particular VEGFR-2, leading to a complex network of signalling pathways resulting in changes to cell permeability, migration and proliferation; unexplored in the lung. We have investigated the downstream signalling mechanisms regulated by VEGF165 in pulmonary and systemic endothelial cells.HUVEC and Human Lung Microvascular Endothelial Cells (HMVEC-L) were treated with VEGF165. Phosphorylations of VEGFR-2 (tyr1175and tyr1214) were measured along with phosphorylation/activation of pMEK1/2, p44/42MAPK (regulating cell proliferation) and eNOS protein (involved in cell permeability). The downstream effects of VEGF165 on cell permeability was assessed by Endohm, Electrical Cell-Substrate Impedance Sensor (ECIS) and FITC-BSA passage and changes in VE-cadherin cell distribution was determined by immunofluorescence.Phosphorylation of VEGFR-2 at tyr1175 and tyr1214 was induced between 2 and 10min (5 fold increase). Activation of pMEK1/2 and p44/42MAPK showed a similar time course to that of VEGFR-2 (>5 fold). Phosphorylation of eNOS was also observed (>2 fold) and indeed VEGF165 increased cell permeability in both cell types (Huvec p<0.001) (Hmvec-l p<0.01) with the different measurement. In both cell types, significant changes in VE-cadherin cellular distribution were generated by VEGF.VEGF165 induces responses in HUVEC and HMVEC-L cell behaviour suggesting different pathways for the regulation of mitogenesis or permeability identifying potential therapeutic targets. %U https://erj.ersjournals.com/content/erj/42/Suppl_57/P4883.full.pdf