Guo Shu-Jie, Zhang Peng, Wu Ling-Yun, Zhang Guan-Nan, Chen Wen-Dong, Gao Ping-Jin
Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Vasc Res. 2016;53(5-6):309-316. doi: 10.1159/000452413. Epub 2016 Dec 15.
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 MF phenotypic modulation caused by Ang II. The decreased level of septin 2 and the increased expression of α-smooth muscle actin (α-SMA), a marker of MFs, were readily observed in Ang II-stimulated MF differentiation. After gene transfer of septin 2, the expression of α-SMA was markedly decreased and the MF migration response to Ang II was inhibited. Furthermore, the inhibition of RhoA, another molecule involved in MF 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-α-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 α-tubulin acetylation, which suggests that septin 2 may serve as a potential therapeutic target for vascular injury.
外膜成纤维细胞（AFs）向肌成纤维细胞（MFs）的表型转化对血管重塑至关重要。研究发现，在血管紧张素II（Ang II）诱导的AFs向MFs分化过程中，Septin 2表达下调；然而，Septin 2在此过程中的作用仍不清楚。在本研究中，我们探究了Septin 2是否参与Ang II引起的外膜MF表型调节。在Ang II刺激的MF分化过程中，很容易观察到Septin 2水平降低以及MF标志物α平滑肌肌动蛋白（α-SMA）表达增加。Septin 2基因转染后，α-SMA的表达明显降低，并且MF对Ang II的迁移反应受到抑制。此外，抑制RhoA（另一个参与MF表型调节的分子）可降低MF的运动性以及Ang II诱导的Septin 2表达。最后，转染Septin 2可恢复MF中乙酰化α微管蛋白的水平。这些发现表明，作为RhoA的下游分子，Septin 2通过保护α微管蛋白乙酰化减弱了AFs对Ang II的反应，这表明Septin 2可能是血管损伤的潜在治疗靶点。
