Endothelial immune activation programmes cell‐fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4‐ERK‐FOXC2 signalling

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12835-list-0001">The mechanisms by which bacteria alter endothelial cell phenotypes and programme inflammatory angiogenesis remain unclear.In lung endothelial cells, we demonstrate that toll‐like receptor 4 (TLR4) signalling induces activation of forkhead box protein C2 (FOXC2), a transcriptional factor implicated in lymphangiogenesis and endothelial specification, in an extracellular signal‐regulated kinase (ERK)‐dependent manner.TLR4‐ERK‐FOXC2 signalling regulates expression of the Notch ligand DLL4 and signals inflammatory angiogenesis in vivo and in vitro.Our work reveals a novel link between endothelial immune signalling (TLR pathway) and a vascular transcription factor, FOXC2, that regulates embryonic vascular development.This mechanism is likely to be relevant to pathological angiogenesis complicating inflammatory diseases in humans.