期刊
BIOMED RESEARCH INTERNATIONAL
卷 2015, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2015/965271
关键词
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资金
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR)
- Agenzia Spaziale Italiana
- Fondazione Roma
Angiopoietins are vascular factors essential for blood vessel assembly and correct organization and maturation. This study describes a novel calcium-dependent machinery activated through Angiopoietin-1/2-Tie receptor system in HUVECs monolayer. Both cytokines were found to elicit intracellular calcium mobilization. Targeting intracellular Ca2+ signaling, antagonizing IP3 with 2-APB or cADPR with 8Br-cADPR, was found to modulate in vitro angiogenic responses to Angiopoietins in a specific way. 2-APB and 8Br-cADPR impaired the phosphorylation of AKT and FAK induced by Ang-1 and Ang-2. On the other hand, phosphorylation of ERK1/2 and p38, as well as cell proliferation, was not affected by either inhibitor. The ability of ECs to migrate following Angs stimulation, evaluated by scratch assay, was reduced by either 2-APB or 8Br-cADPR following Ang-2 stimulation and only slightly affected by 2-APB in cells stimulated with Ang-1. These results identify a novel calcium-dependent machinery involved in the complex interplay regulating angiogenic processes showing that IP3 -and cADPR-induced Ca2+ release specifically regulates distinct Angs-mediated angiogenic steps.
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