title: The pro-angiogenic activity of urotensin-II on human vascular endothelial cells involves ERK1/2 and PI3K signaling pathways.
abstract: Human vascular endothelial cells express the urotensin-II (U-II) receptor and exhibit a strong in vitro angiogenic response to the peptide. Thus, in the present study an in vitro model, based on human umbilical vein endothelial cells (HUVEC) cultured on Matrigel, was used to characterize more in detail the signaling pathways that control the pro-angiogenic action of U-II. The activation of the U-II receptor (UT) was associated with an increase of intracellular calcium concentration. Both calcium rise and pro-angiogenic effect of the peptide can be blocked by U73122, a selective inhibitor of phospholipase-C, indicating that the signal transduction from UT mainly involves the phospholipase-C/IP(3) pathway. As far as the downstream signaling pathways are concerned, western blot analyses and experiments with specific inhibitors indicated that the U-II-induced self-organization of the cells into capillary-like structures was PKC dependent and involved the activation of the ERK1/2, but not p38-MAPK, transduction pathway. Interestingly, the pharmacological inhibition of PI3K (obtained with LY294002), hindered the capacity of U-II to induce a proangiogenic effect on HUVEC, suggesting that PI3K-dependent pathways also play a role in regulating the process.
authors.affiliation: Departments of Human Anatomy and Physiology (Section of Anatomy), University of Padova Medical School, Padova, Italy. diego.guidolin@unipd.it
authors.forename: Diego
authors.initials: D
authors.lastname: Guidolin
authors.forename: Giovanna
authors.initials: G
authors.lastname: Albertin
authors.forename: Barbara
authors.initials: B
authors.lastname: Oselladore
authors.forename: Elisa
authors.initials: E
authors.lastname: Sorato
authors.forename: Piera
authors.initials: P
authors.lastname: Rebuffat
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mascarin
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014579:Urotensins / Q000502:physiology*
chemical_list: D014579:Urotensins; C029677:urotensin II; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases