Tie1: an orphan receptor provides context for angiopoietin-2/Tie2 signaling

Tie‐ing Up Angiogenesis to Treat Nonalcoholic Steatohepatitis

“…This dual role is explained in part because Tie1 is considered an orphan receptor with no naturally identified ligand but rather modulates ANG signaling through Tie2. (6) ANG1 signaling through Tie1/Tie2 promotes normal vascular homeostasis under basal (i.e., noninflammatory) conditions; but in the setting of inflammatory mediators the Tie1 receptor undergoes cleavage of its ectodomain, and ANG2 Abbreviations: ANG, angiopoietin; CD, cluster of differentiation; HCC, hepatocellular cancer; MCD, methioninecholine-deficient; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; Tie, tyrosine kinase with immunoglobulin and epidermal growth factor homology domains; VEGF, vascular endothelial growth factor. then becomes the dominant angiogenic signal, where it functions as a Tie2 antagonist and promotes a neoangiogenic, abnormal vasculature, prone to increased leakage.…”

“…Angiopoietins (principally ANG1 and ANG2) function by signaling through Tie receptors to regulate normal developmental angiogenesis and, depending on the circumstances (described below), as either context‐dependent agonists or antagonists of Tie2 signaling. This dual role is explained in part because Tie1 is considered an orphan receptor with no naturally identified ligand but rather modulates ANG signaling through Tie2 . ANG1 signaling through Tie1/Tie2 promotes normal vascular homeostasis under basal (i.e., noninflammatory) conditions; but in the setting of inflammatory mediators the Tie1 receptor undergoes cleavage of its ectodomain, and ANG2 then becomes the dominant angiogenic signal, where it functions as a Tie2 antagonist and promotes a neoangiogenic, abnormal vasculature, prone to increased leakage .…”

Tie2 protects the vasculature against thrombus formation in systemic inflammation

“…Tie2 is stimulated by Angpt-1, a protein secreted by periendothelial cells and platelets. In the context of inflammation, a paralog of Angpt-1 called Angpt-2 competitively inhibits Tie2 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32). While several groups have shown that the Angpt/Tie2 pathway becomes dysregulated in human sepsis (reviewed in ref.…”

Role and regulation of growth plate vascularization during coupling with osteogenesis in tibial dyschondroplasia of chickens

“…Among these, vasculogenesis refers to the de novo emergence of a vascular network to initiate the formation of blood islands from mesodermal progenitors to hemangioblasts, followed by migration and association of endothelial cells to form a primitive capillary plexus 14 , 15 , whereas angiogenesis refers to the generation of vessels by sprouting or non-sprouting from pre-existing capillaries 12 . In this process, a variety of angiogenic factors, including vascular endothelial growth factor (VEGF) and its receptors 16 – 18 , the fibroblast growth factor (FGF) family 19 , platelet-derived growth factor (PDGF)-BB and its receptor 20 , 21 , angiopoietin-1 (Ang1), Ang2 and their endothelium-specific receptors such as tyrosine kinase Tie2 (also known as Tek) 22 , 23 , are all widely expressed as primary inducers of vascular development and postnatal angiogenesis 24 , 25 . Among these, blockage of the VEGF receptors VEGFR1 and VEGFR2 contributes to decreased blood vessel formation and bone regeneration 17 .…”