HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells

Lingfang Zeng, Qingzhong Xiao, Andriana Margariti, Zhongyi Zhang, Anna Zampetaki, Seema Patel, Maurizio C. Capogrossi, Yanhua Hu, Qingbo Xu

Research output: Contribution to journalArticle

Abstract

Reendothelialization involves endothelial progenitor cell (EPC) homing, proliferation, and differentiation, which may be influenced by fluid shear stress and local flow pattern. This study aims to elucidate the role of laminar flow on embryonic stem (ES) cell differentiation and the underlying mechanism. We demonstrated that laminar flow enhanced ES cell-derived progenitor cell proliferation and differentiation into endothelial cells (ECs). Laminar flow stabilized and activated histone deacetylase 3 (HDAC3) through the Flk-1-PI3K-Akt pathway, which in turn deacetylated p53, leading to p21 activation. A similar signal pathway was detected in vascular endothelial growth factor-induced EC differentiation. HDAC3 and p21 were detected in blood vessels during embryogenesis. Local transfer of ES cell-derived EPC incorporated into injured femoral artery and reduced neointima formation in a mouse model. These data suggest that shear stress is a key regulator for stem cell differentiation into EC, especially in EPC differentiation, which can be used for vascular repair, and that the Flk-1-PI3K-Akt-HDAC3-p53-p21 pathway is crucial in such a process.

Original languageEnglish
Pages (from-to)1059-1069
Number of pages11
JournalJournal of Cell Biology
Volume174
Issue number7
DOIs
Publication statusPublished - Sep 25 2006

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Vascular Endothelial Growth Factor A
Cell Differentiation
Stem Cells
Endothelial Cells
Embryonic Stem Cells
Phosphatidylinositol 3-Kinases
Blood Vessels
Cell Proliferation
Neointima
Femoral Artery
Embryonic Development
histone deacetylase 3
Signal Transduction
Endothelial Progenitor Cells

ASJC Scopus subject areas

  • Cell Biology

Cite this

Zeng, L., Xiao, Q., Margariti, A., Zhang, Z., Zampetaki, A., Patel, S., ... Xu, Q. (2006). HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. Journal of Cell Biology, 174(7), 1059-1069. https://doi.org/10.1083/jcb.200605113

HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. / Zeng, Lingfang; Xiao, Qingzhong; Margariti, Andriana; Zhang, Zhongyi; Zampetaki, Anna; Patel, Seema; Capogrossi, Maurizio C.; Hu, Yanhua; Xu, Qingbo.

In: Journal of Cell Biology, Vol. 174, No. 7, 25.09.2006, p. 1059-1069.

Research output: Contribution to journalArticle

Zeng, L, Xiao, Q, Margariti, A, Zhang, Z, Zampetaki, A, Patel, S, Capogrossi, MC, Hu, Y & Xu, Q 2006, 'HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells', Journal of Cell Biology, vol. 174, no. 7, pp. 1059-1069. https://doi.org/10.1083/jcb.200605113
Zeng, Lingfang ; Xiao, Qingzhong ; Margariti, Andriana ; Zhang, Zhongyi ; Zampetaki, Anna ; Patel, Seema ; Capogrossi, Maurizio C. ; Hu, Yanhua ; Xu, Qingbo. / HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. In: Journal of Cell Biology. 2006 ; Vol. 174, No. 7. pp. 1059-1069.
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