Abstract
Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to sites of tissue regeneration to sustain neovascularization and reendothelialization after acute vascular injury. This feature makes them particularly suitable for cell-based therapy. In mature endothelium, store-operated Ca2+ entry (SOCE) is activated following emptying of inositol-1,4,5-trisphosphate-sensitive stores, and controls a wide number of functions, including proliferation, nitric oxide synthesis, and vascular permeability. The present work aimed at investigating SOCE expression in EPCs harvested from both peripheral blood (PB-EPCs) and umbilical cord blood (UCB-EPCs) by employing both Ca2+ imaging and molecular biology techniques. SOCE was induced upon either pharmacological (ie, cyclopiazonic acid) or physiological (ie, ATP) depletion of the intracellular Ca2+ pool. Further, store-dependent Ca2+ entry was inhibited by the SOCE inhibitor, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2, 3-thiadiazole-5-carboxamide (BTP-2). Real-time reverse transcription-polymerase chain reaction and western blot analyses showed that both PB-EPCs and UCB-EPCs express all the molecular candidates to mediate SOCE in differentiated cells, including TRPC1, TRPC4, Orai1, and Stim1. Moreover, pharmacological maneuvers demonstrated that, as well as in differentiated endothelial cells, the signal transduction pathway leading to depletion of the intracellular Ca2+ pool impinged on the phospholipase C/inositol-1,4,5-trisphosphate pathway. Finally, blockage of SOCE with BTP-2 impaired PB-EPC proliferation. These findings provide the first evidence that EPCs express SOCE, which might thus be regarded as a novel target to enhance the regenerative outcome of cell-based therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 1967-1981 |
| Number of pages | 15 |
| Journal | Stem Cells and Development |
| Volume | 19 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2010 |
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ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Hematology
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Store-operated Ca2+ entry is expressed in human endothelial progenitor cells. / Sánchez-Hernández, Yuly; Laforenza, Umberto; Bonetti, Elisa; Fontana, Jacopo; Dragoni, Silvia; Russo, Marika; Avelino-Cruz, José Everardo; Schinelli, Sergio; Testa, Domenico; Guerra, Germano; Rosti, Vittorio; Tanzi, Franco; Moccia, Francesco.
In: Stem Cells and Development, Vol. 19, No. 12, 01.12.2010, p. 1967-1981.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Store-operated Ca2+ entry is expressed in human endothelial progenitor cells
AU - Sánchez-Hernández, Yuly
AU - Laforenza, Umberto
AU - Bonetti, Elisa
AU - Fontana, Jacopo
AU - Dragoni, Silvia
AU - Russo, Marika
AU - Avelino-Cruz, José Everardo
AU - Schinelli, Sergio
AU - Testa, Domenico
AU - Guerra, Germano
AU - Rosti, Vittorio
AU - Tanzi, Franco
AU - Moccia, Francesco
PY - 2010/12/1
Y1 - 2010/12/1
N2 - Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to sites of tissue regeneration to sustain neovascularization and reendothelialization after acute vascular injury. This feature makes them particularly suitable for cell-based therapy. In mature endothelium, store-operated Ca2+ entry (SOCE) is activated following emptying of inositol-1,4,5-trisphosphate-sensitive stores, and controls a wide number of functions, including proliferation, nitric oxide synthesis, and vascular permeability. The present work aimed at investigating SOCE expression in EPCs harvested from both peripheral blood (PB-EPCs) and umbilical cord blood (UCB-EPCs) by employing both Ca2+ imaging and molecular biology techniques. SOCE was induced upon either pharmacological (ie, cyclopiazonic acid) or physiological (ie, ATP) depletion of the intracellular Ca2+ pool. Further, store-dependent Ca2+ entry was inhibited by the SOCE inhibitor, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2, 3-thiadiazole-5-carboxamide (BTP-2). Real-time reverse transcription-polymerase chain reaction and western blot analyses showed that both PB-EPCs and UCB-EPCs express all the molecular candidates to mediate SOCE in differentiated cells, including TRPC1, TRPC4, Orai1, and Stim1. Moreover, pharmacological maneuvers demonstrated that, as well as in differentiated endothelial cells, the signal transduction pathway leading to depletion of the intracellular Ca2+ pool impinged on the phospholipase C/inositol-1,4,5-trisphosphate pathway. Finally, blockage of SOCE with BTP-2 impaired PB-EPC proliferation. These findings provide the first evidence that EPCs express SOCE, which might thus be regarded as a novel target to enhance the regenerative outcome of cell-based therapy.
AB - Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to sites of tissue regeneration to sustain neovascularization and reendothelialization after acute vascular injury. This feature makes them particularly suitable for cell-based therapy. In mature endothelium, store-operated Ca2+ entry (SOCE) is activated following emptying of inositol-1,4,5-trisphosphate-sensitive stores, and controls a wide number of functions, including proliferation, nitric oxide synthesis, and vascular permeability. The present work aimed at investigating SOCE expression in EPCs harvested from both peripheral blood (PB-EPCs) and umbilical cord blood (UCB-EPCs) by employing both Ca2+ imaging and molecular biology techniques. SOCE was induced upon either pharmacological (ie, cyclopiazonic acid) or physiological (ie, ATP) depletion of the intracellular Ca2+ pool. Further, store-dependent Ca2+ entry was inhibited by the SOCE inhibitor, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2, 3-thiadiazole-5-carboxamide (BTP-2). Real-time reverse transcription-polymerase chain reaction and western blot analyses showed that both PB-EPCs and UCB-EPCs express all the molecular candidates to mediate SOCE in differentiated cells, including TRPC1, TRPC4, Orai1, and Stim1. Moreover, pharmacological maneuvers demonstrated that, as well as in differentiated endothelial cells, the signal transduction pathway leading to depletion of the intracellular Ca2+ pool impinged on the phospholipase C/inositol-1,4,5-trisphosphate pathway. Finally, blockage of SOCE with BTP-2 impaired PB-EPC proliferation. These findings provide the first evidence that EPCs express SOCE, which might thus be regarded as a novel target to enhance the regenerative outcome of cell-based therapy.
UR - http://www.scopus.com/inward/record.url?scp=78649705406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649705406&partnerID=8YFLogxK
U2 - 10.1089/scd.2010.0047
DO - 10.1089/scd.2010.0047
M3 - Article
C2 - 20677912
AN - SCOPUS:78649705406
VL - 19
SP - 1967
EP - 1981
JO - Stem Cells and Development
JF - Stem Cells and Development
SN - 1547-3287
IS - 12
ER -