PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation model

The current study investigated the effects of the granulocyte-macrophage colony-stimulating factor (GM-CSF) on rat endothelial progenitor cell (EPC) biology. EPCs were isolated from rat bone marrow and experiments were carried out to determine the dose- and time-dependent effects of GM-CSF on angi...

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Main Authors: Wei Zhao, Xiang-Hong Yang
Format: Article
Language:English
Published: Academy of Science of South Africa 2010-06-01
Series:South African Journal of Science
Subjects:
Online Access:https://sajs.co.za/article/view/10150
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author Wei Zhao
Xiang-Hong Yang
author_facet Wei Zhao
Xiang-Hong Yang
author_sort Wei Zhao
collection DOAJ
description The current study investigated the effects of the granulocyte-macrophage colony-stimulating factor (GM-CSF) on rat endothelial progenitor cell (EPC) biology. EPCs were isolated from rat bone marrow and experiments were carried out to determine the dose- and time-dependent effects of GM-CSF on angiogenesis, proliferation, viability, migration and vasculogenesis. EPCs were co- cultured with rat cardiac microvascular endothelial cells (CMECs) to determine the effect of GM- CSF on EPC angiogenesis in vitro. EPC proliferation and viability, migration, and vasculogenesis were measured by the respective application of the method of transcription and translation (MTT) assay, the Transwell chamber assay and the Matrigel assay. GM-CSF treatment stimulated EPC angiogenesis, proliferation, viability, migration and tubule formation in a dose- and time-dependent manner. Furthermore, GM-CSF treatment led to the upregulation of integrinβ2, vascular endothelial growth factor (VEGF) and p-extracellular signal-regulated kinase (p-ERK) 1/2 levels in EPCs. Moreover, two different phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 and Wortmannin) partially inhibited the GM-CSF-mediated increase in p-ERK1/2 levels in EPCs. The ERK inhibitor, FR180204, dramatically inhibited GM-CSF-mediated stimulation of EPC proliferation, migration and vasculogenesis. Taken together, the results of the current study provide evidence that a PI3K-dependent ERK signalling pathway is, at least, partially responsible for the GM-CSF-mediated effects on EPC function.
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spelling doaj-art-ea2bae6ee9bf4696927fb1a7a48f22ee2025-08-20T02:25:59ZengAcademy of Science of South AfricaSouth African Journal of Science1996-74892010-06-011065/69 pages9 pages8352PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation modelWei Zhao0Xiang-Hong Yang1Department of Pathology, Affiliated Shengjing Hospital, China Medical UniversityDepartment of Pathology, Affiliated Shengjing Hospital, China Medical UniversityThe current study investigated the effects of the granulocyte-macrophage colony-stimulating factor (GM-CSF) on rat endothelial progenitor cell (EPC) biology. EPCs were isolated from rat bone marrow and experiments were carried out to determine the dose- and time-dependent effects of GM-CSF on angiogenesis, proliferation, viability, migration and vasculogenesis. EPCs were co- cultured with rat cardiac microvascular endothelial cells (CMECs) to determine the effect of GM- CSF on EPC angiogenesis in vitro. EPC proliferation and viability, migration, and vasculogenesis were measured by the respective application of the method of transcription and translation (MTT) assay, the Transwell chamber assay and the Matrigel assay. GM-CSF treatment stimulated EPC angiogenesis, proliferation, viability, migration and tubule formation in a dose- and time-dependent manner. Furthermore, GM-CSF treatment led to the upregulation of integrinβ2, vascular endothelial growth factor (VEGF) and p-extracellular signal-regulated kinase (p-ERK) 1/2 levels in EPCs. Moreover, two different phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 and Wortmannin) partially inhibited the GM-CSF-mediated increase in p-ERK1/2 levels in EPCs. The ERK inhibitor, FR180204, dramatically inhibited GM-CSF-mediated stimulation of EPC proliferation, migration and vasculogenesis. Taken together, the results of the current study provide evidence that a PI3K-dependent ERK signalling pathway is, at least, partially responsible for the GM-CSF-mediated effects on EPC function.https://sajs.co.za/article/view/10150co-culture modelendothelial progenitor cellextracellular signal-regulated kinasegranulocyte-macrophage colony-stimulating factorneovascularisationphosphatidylinositol 3-kinase
spellingShingle Wei Zhao
Xiang-Hong Yang
PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation model
South African Journal of Science
co-culture model
endothelial progenitor cell
extracellular signal-regulated kinase
granulocyte-macrophage colony-stimulating factor
neovascularisation
phosphatidylinositol 3-kinase
title PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation model
title_full PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation model
title_fullStr PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation model
title_full_unstemmed PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation model
title_short PI3K-dependent ERK is involved in GM-CSF-mediated activation of progenitor cells in a neovascularisation model
title_sort pi3k dependent erk is involved in gm csf mediated activation of progenitor cells in a neovascularisation model
topic co-culture model
endothelial progenitor cell
extracellular signal-regulated kinase
granulocyte-macrophage colony-stimulating factor
neovascularisation
phosphatidylinositol 3-kinase
url https://sajs.co.za/article/view/10150
work_keys_str_mv AT weizhao pi3kdependenterkisinvolvedingmcsfmediatedactivationofprogenitorcellsinaneovascularisationmodel
AT xianghongyang pi3kdependenterkisinvolvedingmcsfmediatedactivationofprogenitorcellsinaneovascularisationmodel