Adenovirus-Mediated Overexpression of Septin 2 Attenuates α-Smooth Muscle Actin Expression and Adventitial Myofibroblast Migration Induced by Angiotensin II

作者：Guo, Shu-Jie; Zhang, Peng; Wu, Ling-Yun; Zhang, Guan-Nan; Chen, Wen-Dong; Gao, Ping-Jin^*

来源：Journal of Vascular Research, 2016, 53(5-6): 309-316.

DOI：10.1159/000452413

• Adventitial fibroblasts
• Myofibroblasts
• Phenotype transformation
• Septin 2
• Angiotensin II
• Migration

Phenotypic transformation from adventitial fibroblasts (AFs) to myofibroblasts (MFs) is critical for vascular remodeling. Septin 2 was found to be downregulated during the differentiation of AFs to MFs induced by angiotensin II (Ang II); however, the role of septin 2 in this process is still unknown. In this study, we investigate whether septin 2 contributes to the adventitial ME phenotypic modulation caused by Ang II. The decreased level of septin 2 and the increased expression of alpha-smooth muscle actin (alpha-SMA), a marker of MFs, were readily observed in Ang II-stimulated ME differentiation. After gene transfer of septin 2, the expression of alpha-SMA was markedly decreased and the ME migration response to Ang II was inhibited. Furthermore, the inhibition of RhoA, another molecule involved in ME phenotypic modulation, decreased the motility of MFs and the expression of septin 2 triggered in Ang II. Finally, transfection of septin 2 rescued the level of acetyl-alpha-tubulin in MFs. These findings demonstrate that, as a downstream molecule of RhoA, septin 2 blunted the responses of AFs to Ang II by protecting alpha-tubulin acetylation, which suggests that septin 2 may serve as a potential therapeutic target for vascular injury.

• 出版日期2016
• 单位中国中医科学院; 上海交通大学; 上海市闵行区中心医院; 中国中医科学院西苑医院