Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.
Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.
复制标题
DOI：
10.1155/2018/6712585
复制
发表时间：
2018
影响因子：
--
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Chen T;Li M;Fan X;Cheng J;Wang L
心房成纤维细胞向肌成纤维细胞的分化在心房纤维化中起着关键作用。丹参酮IIA磺酸钠(DS-201)是丹参酮IIA的一种水溶性衍生物，已被证明具有强大的抗纤维化特性。然而，DS-201对血管紧张素II-(Ang II-)诱导的心房成纤维细胞向肌成纤维细胞分化的保护作用尚不清楚。在本研究中，血管紧张素转换酶II在存在或不存在DS-201的情况下刺激人心房成纤维细胞。检测α-平滑肌肌动蛋白(α-SMA)、I型胶原和III型胶原的表达及活性氧(ROS)的产生。检测转化生长因子-β-1(转化生长因子-β-1)的表达及其下游信号转导通路，如Smad2/3的磷酸化。结果表明，DS-201显著抑制血管紧张素Ⅱ诱导的人心房成纤维细胞迁移，降低血管紧张素Ⅱ诱导的α-SMA、I型胶原和III型胶原的表达。DS-201还能显著抑制血管紧张素Ⅱ刺激的ROS生成和转化生长因子-β-1的表达。与这些结果一致，DS-201显著抑制Ang II诱导的Smad2/3的磷酸化和Periostin的表达。这些结果以及抗氧化剂N-乙酰半胱氨酸和抗转化生长因子-β-1抗体的实验表明，DS-201至少部分地通过抑制氧化应激和抑制转化生长因子-β-1信号通路的激活来阻止血管紧张素II诱导的心房成纤维细胞向肌成纤维细胞分化。所有这些数据表明DS-201在治疗心肌纤维化方面具有潜在的应用价值。
Differentiation of atrial fibroblasts into myofibroblasts plays a critical role in atrial fibrosis. Sodium tanshinone IIA sulfonate (DS-201), a water-soluble derivative of tanshinone IIA, has been shown to have potent antifibrotic properties. However, the protective effects of DS-201 on angiotensin II- (Ang II-) induced differentiation of atrial fibroblasts into myofibroblasts remain to be elucidated. In this study, human atrial fibroblasts were stimulated with Ang II in the presence or absence of DS-201. Then, α-smooth muscle actin (α-SMA), collagen I, and collagen III expression and reactive oxygen species (ROS) generation were measured. The expression of transforming growth factor-β1 (TGF-β1) and the downstream signaling of TGF-β1, such as phosphorylation of Smad2/3, were also determined. The results demonstrated that DS-201 significantly prevented Ang II-induced human atrial fibroblast migration and decreased Ang II-induced α-SMA, collagen I, and collagen III expression. Furthermore, increased production of ROS and expression of TGF-β1 stimulated by Ang II were also significantly inhibited by DS-201. Consistent with these results, DS-201 significantly inhibited Ang II-evoked Smad2/3 phosphorylation and periostin expression. These results and the experiments involving N-acetyl cysteine (antioxidant) and an anti-TGF-β1 antibody suggest that DS-201 prevent Ang II-induced differentiation of atrial fibroblasts to myofibroblasts, at least in part, through suppressing oxidative stress and inhibiting the activation of TGF-β1 signaling pathway. All of these data indicate the potential utility of DS-201 for the treatment of cardiac fibrosis.
登录
查看更多内容
影响因子：
7.2
作者：
Ahn, Young-Min;Kim, Su Kang;Lee, Byung-Cheol
通讯作者：
Lee, Byung-Cheol
二甲双胍抑制血管紧张素 II 诱导的心肌成纤维细胞分化为肌成纤维细胞
影响因子：
3.7
作者：
Bai J;Zhang N;Hua Y;Wang B;Ling L;Ferro A;Xu B
通讯作者：
Xu B
中医药治疗肺纤维化的进展与未来展望
影响因子：
5.4
作者：
Li LC;Kan LD
通讯作者：
Kan LD
影响因子：
5.6
作者：
Li, Wei;Zhang, Yu;Zhang, Mengyuan
通讯作者：
Zhang, Mengyuan
影响因子：
5
作者：
Chen, Wenying;Tang, Futian;Liu, Peiqing
通讯作者：
Liu, Peiqing