Endothelial colony-forming cells (ECFCs) are the only endothelial progenitor cells (EPCs) that are capable of acquiring a mature endothelial phenotype. ECFCs are mainly mobilized from bone marrow to promote vascularization and represent a promising tool for cell-based therapy of severe ischemic diseases. Vascular endothelial growth factor (VEGF) stimulates the proliferation of peripheral blood-derived ECFCs (PB-ECFCs) through oscillations in intracellular Ca2+ concentration ([Ca2+]i). VEGF-induced Ca2+ spikes are driven by the interplay between inositol-1,4,5-trisphosphate (InsP3)-dependent Ca2+ release and store-operated Ca2+ entry (SOCE). The therapeutic potential of umbilical cord blood-derived ECFCs (UCB-ECFCs) has also been shown in recent studies. However, VEGF-induced proliferation of UCB-ECFCs is faster compared with their peripheral counterpart. Unlike PB-ECFCs, UCB-ECFCs express canonical transient receptor potential channel 3 (TRPC3) that mediates diacylglycerol-dependent Ca2+ entry. The present study aimed at investigating whether the higher proliferative potential of UCB-ECFCs was associated to any difference in the molecular underpinnings of their Ca 2+ response to VEGF. We found that VEGF induces oscillations in [Ca2+]i that are patterned by the interaction between InsP3-dependent Ca2+ release and SOCE. Unlike PB-ECFCs, VEGF-evoked Ca2+ oscillations do not arise in the absence of extracellular Ca2+ entry and after pharmacological (with Pyr3 and flufenamic acid) and genetic (by employing selective small interference RNA) suppression of TRPC3. VEGF-induced UCB-ECFC proliferation is abrogated on inhibition of the intracellular Ca2+ spikes. Therefore, the Ca 2+ response to VEGF in UCB-ECFCs is shaped by a different Ca 2+ machinery as compared with PB-ECFCs, and TRPC3 stands out as a promising target in EPC-based treatment of ischemic pathologies. © Mary Ann Liebert, Inc.
Canonical transient receptor potential 3 channel triggers vascular endothelial growth factor-induced intracellular Ca2+ oscillations in endothelial progenitor cells isolated from umbilical cord blood / S. Dragoni, U. Laforenza, E. Bonetti, F. Lodola, C. Bottino, G. Guerra, A. Borghesi, M. Stronati, V. Rosti, F. Tanzi, F. Moccia. - In: STEM CELLS AND DEVELOPMENT. - ISSN 1547-3287. - 22:19(2013), pp. 2561-2580.
|Titolo:||Canonical transient receptor potential 3 channel triggers vascular endothelial growth factor-induced intracellular Ca2+ oscillations in endothelial progenitor cells isolated from umbilical cord blood|
|Parole Chiave:||Adult; Anti-Inflammatory Agents; Calcium; Cell Proliferation; Cells, Cultured; Endothelial Cells; Female; Fetal Blood; Flufenamic Acid; Humans; Inositol 1,4,5-Trisphosphate; Ion Transport; Middle Aged; Neovascularization, Physiologic; Pyrazoles; RNA Interference; RNA, Small Interfering; Signal Transduction; Stem Cells; TRPC Cation Channels; Vascular Endothelial Growth Factor A; Young Adult|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||1-ott-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1089/scd.2013.0032|
|Appare nelle tipologie:||01 - Articolo su periodico|