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Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease.

Makinde T, Agrawal DK - J. Cell. Mol. Med. (2008)

Bottom Line: Angiopoietin-1 (Ang-1) is the primary agonist for Tie2 tyrosine kinase receptor (Tie2), and the effect of Ang-1-Tie2 signalling is context-dependent.Ang-1 has an anti-inflammatory effect, when co-localized with vascular endothelial growth factor (VEGF) in the vasculature.In this article, we have summarized and critically reviewed the pathophysiological role of Ang-1-Tie2 signalling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.

ABSTRACT
Angiopoietin-1 (Ang-1) is the primary agonist for Tie2 tyrosine kinase receptor (Tie2), and the effect of Ang-1-Tie2 signalling is context-dependent. Deficiency in either Ang-1 or Tie2 protein leads to severe microvascular defects and subsequent embryonic lethality in murine model. Tie2 receptors are expressed in several cell types, including endothelial cells, smooth muscle cells, fibroblasts, epithelial cells, monocytes, neutrophils, eosinophils and glial cells. Ang-1-Tie2 signalling induces a chemotactic effect in smooth muscle cells, neutrophils and eosinophils, and induces differentiation of mesenchymal cells to smooth muscle cells. Additionally, this signalling pathway induces the secretion of serotonin, matrix metalloproteinases (MMPs) and plasmin. Ang-1 inhibits the secretion of tissue inhibitor of matrix metalloproteinase (TIMPs). Aberrant expression and activity of Tie2 in vascular and non-vascular cells may result in the development of rheumatoid arthritis, cancer, hypertension and psoriasis. Ang-1 has an anti-inflammatory effect, when co-localized with vascular endothelial growth factor (VEGF) in the vasculature. Thus, Ang-1 could be potentially important in the therapy of various pathological conditions such as pulmonary hypertension, arteriosclerosis and diabetic retinopathy. In this article, we have summarized and critically reviewed the pathophysiological role of Ang-1-Tie2 signalling pathway.

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Related in: MedlinePlus

Schematic depiction of Ang-1-Tie2 effect on various cell types. Several cells are capable expression Ang-1 and Tie2 receptors. Ang-1 is activates Tie2 receptors on these cells, leading to downstream signallingsignaling and ultimately regulation of cellular behavioursbehaviors. Some of the various known roles of Ang-1-Tie2 effects in vascular and extravascular cells have been illustrated.
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fig03: Schematic depiction of Ang-1-Tie2 effect on various cell types. Several cells are capable expression Ang-1 and Tie2 receptors. Ang-1 is activates Tie2 receptors on these cells, leading to downstream signallingsignaling and ultimately regulation of cellular behavioursbehaviors. Some of the various known roles of Ang-1-Tie2 effects in vascular and extravascular cells have been illustrated.

Mentions: Ang-1-Tie2 signalling is required during postnatal bone marrow haematopoiesis. Tie2 and Tie1 expression have been found in some haematopoietic cells [107–111]. Tie2 deficient mice exhibit severely impaired haematopoiesis. On the contrary, some studies showed that Tie2 is not required for embryonic haematopoiesis [109, 112–114]. Ang-1-Tie2 plays a role in maintaining haematopoietic stem cells in the quiescent state in the bone marrow. This role is associated with increased adhesion of Tie2-positive stem cells to Ang-1 expressing osteoblast [109, 115]. Ang-1 and 2 activated growth and migration in Tie2 positive trophoblast during placental development [116]. Tie2 expression is also localized to primary cilia of the surface epithelium of the ovary, bursa and extrao-varian rete duct, as well as to motile cilia of the oviduct, suggesting a role for Tie2 signalling in these cells [117]. A subset of Tie2 expressing monocytes accounts for 2–7% of mononuclear cells in a healthy person. An in vitro study demonstrated Ang-2-mediated migration of this subset of monocytes [118]. Ang-1-Tie2 signalling promotes neural outgrowth from dorsal root ganglion cells. Tie2 expression has been discovered in certain neuronal cells. Tie2 signal transduction elicits neuroprotective effects and a mitogenic effect in vitro (Fig. 3) [23, 119–121]. Overexpression of Ang-1 in the forebrain led to increased vascularization as well as changes in dendrite organization of the neurons [122]. Because Tie2 expression has not been observed in vivo, it is that Ang-1 effects might be integrin mediated. This is consistent with the evidence that Ang-1 is able to inter act with certain integrins to activate downstream signalling [88, 89].


Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease.

Makinde T, Agrawal DK - J. Cell. Mol. Med. (2008)

Schematic depiction of Ang-1-Tie2 effect on various cell types. Several cells are capable expression Ang-1 and Tie2 receptors. Ang-1 is activates Tie2 receptors on these cells, leading to downstream signallingsignaling and ultimately regulation of cellular behavioursbehaviors. Some of the various known roles of Ang-1-Tie2 effects in vascular and extravascular cells have been illustrated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401129&req=5

fig03: Schematic depiction of Ang-1-Tie2 effect on various cell types. Several cells are capable expression Ang-1 and Tie2 receptors. Ang-1 is activates Tie2 receptors on these cells, leading to downstream signallingsignaling and ultimately regulation of cellular behavioursbehaviors. Some of the various known roles of Ang-1-Tie2 effects in vascular and extravascular cells have been illustrated.
Mentions: Ang-1-Tie2 signalling is required during postnatal bone marrow haematopoiesis. Tie2 and Tie1 expression have been found in some haematopoietic cells [107–111]. Tie2 deficient mice exhibit severely impaired haematopoiesis. On the contrary, some studies showed that Tie2 is not required for embryonic haematopoiesis [109, 112–114]. Ang-1-Tie2 plays a role in maintaining haematopoietic stem cells in the quiescent state in the bone marrow. This role is associated with increased adhesion of Tie2-positive stem cells to Ang-1 expressing osteoblast [109, 115]. Ang-1 and 2 activated growth and migration in Tie2 positive trophoblast during placental development [116]. Tie2 expression is also localized to primary cilia of the surface epithelium of the ovary, bursa and extrao-varian rete duct, as well as to motile cilia of the oviduct, suggesting a role for Tie2 signalling in these cells [117]. A subset of Tie2 expressing monocytes accounts for 2–7% of mononuclear cells in a healthy person. An in vitro study demonstrated Ang-2-mediated migration of this subset of monocytes [118]. Ang-1-Tie2 signalling promotes neural outgrowth from dorsal root ganglion cells. Tie2 expression has been discovered in certain neuronal cells. Tie2 signal transduction elicits neuroprotective effects and a mitogenic effect in vitro (Fig. 3) [23, 119–121]. Overexpression of Ang-1 in the forebrain led to increased vascularization as well as changes in dendrite organization of the neurons [122]. Because Tie2 expression has not been observed in vivo, it is that Ang-1 effects might be integrin mediated. This is consistent with the evidence that Ang-1 is able to inter act with certain integrins to activate downstream signalling [88, 89].

Bottom Line: Angiopoietin-1 (Ang-1) is the primary agonist for Tie2 tyrosine kinase receptor (Tie2), and the effect of Ang-1-Tie2 signalling is context-dependent.Ang-1 has an anti-inflammatory effect, when co-localized with vascular endothelial growth factor (VEGF) in the vasculature.In this article, we have summarized and critically reviewed the pathophysiological role of Ang-1-Tie2 signalling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.

ABSTRACT
Angiopoietin-1 (Ang-1) is the primary agonist for Tie2 tyrosine kinase receptor (Tie2), and the effect of Ang-1-Tie2 signalling is context-dependent. Deficiency in either Ang-1 or Tie2 protein leads to severe microvascular defects and subsequent embryonic lethality in murine model. Tie2 receptors are expressed in several cell types, including endothelial cells, smooth muscle cells, fibroblasts, epithelial cells, monocytes, neutrophils, eosinophils and glial cells. Ang-1-Tie2 signalling induces a chemotactic effect in smooth muscle cells, neutrophils and eosinophils, and induces differentiation of mesenchymal cells to smooth muscle cells. Additionally, this signalling pathway induces the secretion of serotonin, matrix metalloproteinases (MMPs) and plasmin. Ang-1 inhibits the secretion of tissue inhibitor of matrix metalloproteinase (TIMPs). Aberrant expression and activity of Tie2 in vascular and non-vascular cells may result in the development of rheumatoid arthritis, cancer, hypertension and psoriasis. Ang-1 has an anti-inflammatory effect, when co-localized with vascular endothelial growth factor (VEGF) in the vasculature. Thus, Ang-1 could be potentially important in the therapy of various pathological conditions such as pulmonary hypertension, arteriosclerosis and diabetic retinopathy. In this article, we have summarized and critically reviewed the pathophysiological role of Ang-1-Tie2 signalling pathway.

Show MeSH
Related in: MedlinePlus