Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2017 (2017), Article ID 2957538, 11 pages
https://doi.org/10.1155/2017/2957538
Research Article

Role of Phosphorylated HDAC4 in Stroke-Induced Angiogenesis

1Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
2Graduate School of Nanchang University, Nanchang, China
3Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

Correspondence should be addressed to Yang Wang and Zhi-Feng Deng

Received 27 August 2016; Accepted 1 December 2016; Published 3 January 2017

Academic Editor: Gelin Xu

Copyright © 2017 Juan Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Acetylation or deacetylation of chromatin proteins and transcription factors is part of a complex signaling system that is involved in the control of neurological disorders. Recent studies have demonstrated that histone deacetylases (HDACs) exert protective effects in attenuating neuronal injury after ischemic insults. Class IIa HDAC4 is highly expressed in the brain, and neuronal activity depends on the nucleocytoplasmic shuttling of HDAC4. However, little is known about HDAC4 and its roles in ischemic stroke. In this study, we report that phosphorylation of HDAC4 was remarkably upregulated after stroke and blockade of HDAC4 phosphorylation with GÖ6976 repressed stroke-induced angiogenesis. Phosphorylation of HDAC4 was also increased in endothelial cells hypoxia model and suppression of HDAC4 phosphorylation inhibited the tube formation and migration of endothelial cells in vitro. Furthermore, in addition to the inhibition of angiogenesis, blockade of HDAC4 phosphorylation suppressed the expression of genes downstream of HIF-VEGF signaling in vitro and in vivo. These data indicate that phosphorylated HDAC4 may serve as an important regulator in stroke-induced angiogenesis. The protective mechanism of phosphorylated HDAC4 is associated with HIF-VEGF signaling, implicating a novel therapeutic target in stroke.