Deciphering vascular endothelial cell growth factor/vascular permeability factor signaling to vascular permeability. Inhibition by atrial natriuretic peptide.

摘要: Vascular endothelial cell growth factor (VEGF) was originally described as a potent vascular permeability (VPF) that importantly contributes to pathobiology. The signaling pathways underlie VEGF/VPF-induced are not well defined. Furthermore, endogenous peptides regulate this important VPF function currently unknown. We report here significantly enhances in aortic cells via linked pathway, sequentially involving Src, ERK, JNK, and phosphatidylinositol 3-kinase/AKT. This leads the serine/threonine phosphorylation redistribution of actin tight junction (TJ) proteins, zona occludens-1 occludin, loss barrier architecture. Atrial natriuretic peptide (ANP) inhibited signaling, TJ protein localization, VPF-induced permeability. involved both guanylate cyclase clearance receptors. In vivo, transgenic mice overexpress ANP showed less kinase activation compared with non-transgenic littermates. Thus, acts an anti-permeability by inhibiting functions we define preserving functional morphology.