Data di Pubblicazione:
2009
Citazione:
Oxytocin stimulates in vitro angiogenesis via a Pyk-2/Src-dependent mechanism / M.G. Cattaneo, G. Lucci, L.M. Vicentini. - In: EXPERIMENTAL CELL RESEARCH. - ISSN 0014-4827. - 315:18(2009), pp. 3210-3219.
Abstract:
We previously reported that the hypothalamic hormone oxytocin (OT), best known for its uterotonic activity, also stimulates migration and invasion in human umbilical vein endothelial cells (HUVECs), thus suggesting a possible role for the peptide in the regulation of angiogenesis. We identified the Gq coupling of OT receptors (OTRs) and phospholipase C (PLC) as the main effectors of OT's action in HUVECs. Moreover, the pro-migratory effect of OT required the OTR-induced activation of the phosphatidylinositol-3-kinase (PI-3-K)/AKT/endothelial nitric oxide synthase (eNOS) pathway. To better characterize the proposed pro-angiogenic effect of OT in HUVECs, we have now utilized a three-dimensional (3-D) in vitro angiogenesis assay, and demonstrated that OT stimulates the outgrowth of capillary-like structures from HUVEC spheroids to an extent comparable to that of vascular endothelial growth factor (VEGF). This OT effect was abolished by inhibitors of PLC, PI-3-K and Src kinase. It was also found that OT phosphorylates proline-rich tyrosine kinase-2 (Pyk-2) and Src kinase in a PLC- and calcium-dependent manner. Furthermore, knockdown of Pyk-2 expression by RNA interference markedly impaired Src phosphorylation, migration and endothelial cell sprouting induced by OT. In conclusion, by using a pharmacological and genetic approach, the OT pro-angiogenic action and the cascade of intracellular signals responsible for it were defined by showing for the first time that OT, by interacting with its Gq-coupled receptor, induces HUVEC capillary outgrowth via Pyk-2 phosphorylation, which activates Src which in turn activates the PI-3-K/AKT pathway.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Angiogenesis; Human endothelial cells; Oxytocin; Phospholipase C; Proline-rich kinase-2 (Pyk-2); Src kinase
Elenco autori:
M.G. Cattaneo, G. Lucci, L.M. Vicentini
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