VEGF-PKD1-HDAC7 signaling promotes endothelial progenitor cell migration and tube formation

Abstract

Histone acetylation/deacetylation is a key mechanism for regulating transcription, which plays an important role in the control of gene expression, tissue growth, and development. In particular, histone deacetylase 7 (HDAC7), a member of class IIa HDACs, is crucial in maintaining vascular integrity. Endothelial progenitor cells (EPCs) play an important role in angiogenesis. However, whether HDAC7 plays a role in the processes of EPCs angiogenesis remains unclear. Migration and tube formation were the two major components of EPC angiogenesis. In this study, we show for the first time that HDAC7 silencing weakened the migration and tube formation abilities of EPCs. VEGF-A induced an increase of phospho-HDAC7 and its nuclear export in a time-dependent manner, which could be partly inhibited by protein kinase D1 (PKD1) inhibitor, but not by the PI3K inhibitor or the MEK inhibitor. Our results showed that EPCs involved in the angiogenesis might be controlled by VEGF-PKD1-HDAC7 axis, which regulates the EPCs angiogenesis by PKD1, but not the ERK and PI3K pathway.