Valproic acid regulates Ang II-induced pericyte-myofibroblast trans -differentiation via MAPK/ERK pathway.

作者：Yan Zhang, Feng Gao, Yuan Tang, Jinwen Xiao, Chuanchuan Li, Yu Ouyang, Yuemei Hou · 发表于：PubMed · 年份：2018 · 被引用次数：35 · 研究领域：Histone Deacetylase Inhibitors Research、Peptidase Inhibition and Analysis、Adenosine and Purinergic Signaling

study showed that HDAC inhibitor VPA blocks cardiac fibrosis, and inflammation inhibition was not involved in this process. VPA treatment inhibited Ang II pericyte proliferation, migration and transdifferentiation to myofibroblast. Furthermore, the inhibition of α-SMA expression by VPA was related to reduce phosphorylation of ERK, and a pharmacological inhibitor of MEK suppressed Ang II-induced α-SMA expression. HDAC4 knockdown resulted in inhibiting Ang II-mediated α-SMA expression as well as the phosphorylation of ERK. Moreover, the inhibitors of protein phosphatase 2A and 1 (PP2A and PP1) restored the Ang II-stimulated α-SMA expression from the inhibitory effect of VPA. Together, the current data indicate that the differentiation of pericytes to myofibroblasts is HDAC4 dependent and requires phosphorylation of ERK.