Role of Phosphorylated HDAC4 in Stroke-Induced Angiogenesis.
Role of Phosphorylated HDAC4 in Stroke-Induced Angiogenesis.
复制标题
磷酸化 HDAC4 在中风诱导的血管生成中的作用
DOI：
10.1155/2017/2957538
复制
发表时间：
2017
影响因子：
--
通讯作者：
Deng ZF
中科院分区：
文献类型：
--
作者：
Liu J;Zhou X;Li Q;Zhou SM;Hu B;Hu GW;Niu X;Guo SC;Wang Y;Deng ZF
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.
