Abstract
The tyrosine kinase Tie-2 and its ligands Angiopoietins (Angs) transduce critical signals for angiogenesis in endothelial cells. This receptor and Ang-1 are coexpressed in hematopoietic stem cells and in a subset of megakaryocytes, though a possible role of angiopoietins in megakaryocytic differentiation/proliferation remains to be demonstrated. To investigate a possible effect of Ang-1/Ang-2 on megakaryocytic proliferation/differentiation we have used both normal CD34+ cells induced to megakaryocytic differentiation and the UT7 cells engineered to express the thrombopoietin receptor (TPOR, also known as c-mpl, UT7/mpl). Our results indicate that Ang-1/Ang-2 may have a role in megakaryopoiesis. Particularly, Ang-2 is predominantly produced and released by immature normal megakaryocytic cells and by undifferentiated UT7/mpl cells and slightly stimulated TPO-induced cell proliferation. Ang-1 production is markedly induced during megakaryocytic differentiation/maturation and potentiated TPO-driven megakaryocytic differentiation. Blocking endogenously released angiopoietins partially inhibited megakaryocytic differentiation, particularly for that concerns the process of polyploidization. According to these data it is suggested that an autocrine angiopoietin/Tie-2 loop controls megakaryocytic proliferation and differentiation.
Highlights
Angiopoietins are a family of molecules known to bind to, and activate, the Tie (Tyr kinase with Ig and EGF homology domains) receptors, Tie-1 and Tie-2 receptor on endothelial cells [1]
vascular endothelial growth factor (VEGF) production in megakaryocytic cells is promoted by TPO [26,27] and plays a role in megakaryocytic differentiation and maturation promoted by TPO [28,29]
Few data are available on the expression and function of angiopoietins/Tie-2 in megakaryocytic cells [13,14]
Summary
Angiopoietins are a family of molecules known to bind to, and activate, the Tie (Tyr kinase with Ig and EGF homology domains) receptors, Tie-1 and Tie-2 receptor on endothelial cells [1]. The interaction, at the level of stem cell niches, between quiescent hematopoietic stem cell cells (HSCs, expressing Tie-2) and the endosteal niche (producing Ang-1) induces the cellular adhesion of HSCs to osteoblastic cells, contribute to survival of HSCs and protect stem cells against various types of potentially dangerous cellular stresses [5,6]. These studies have provided evidence that Ang-1 released by osteoblasts plays a critical role in inducing HSC quiescence [5]. Ang-2, the other Tie-2 ligand, known to be an antagonist of Tie-2/Ang-1 signaling in angiogenesis, seems to act as an Ang-1 antagonist at the level of HSCs: while Ang-1 maintained long-term repopulating activity of HSCs, the addition of Ang-2 markedly interfered with the effects of Ang-1 [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
