Dioscin elevates lncRNA MANTIS in therapeutic angiogenesis for heart diseases.
Dioscin elevates lncRNA MANTIS in therapeutic angiogenesis for heart diseases.
复制标题
作者：
Kong C;Lyu D;He C;Li R;Lu Q
薯蓣皂苷在我国已广泛应用于冠心病的临床治疗。然而，薯蓣皂苷介导的心脏保护作用的潜在机制尚未阐明。在这里，我们发现薯蓣皂苷显著挽救心肌梗死（MI）小鼠模型的心脏功能，伴随着心脏纤维化和细胞凋亡的减少，这是由血管生成增加引起的。从机制上讲，薯蓣皂苷通过上调lncRNA MANTIS促进缺氧内皮细胞的增殖和迁移，后者在染色质重塑复合物中充当支架lncRNA。同时，它使pol II与转录起始位点结合，从而诱导血管生成相关基因的表达，包括SOX 18，SMAD 6和COUP‐TFII。相反，IncRNA MANTIS沉默防止薯蓣皂苷诱导的缺氧内皮细胞迁移和血管生成。总之，这些数据提供了新的见解，阐明了薯蓣皂苷对心肌梗死损伤的心脏保护作用，并证实了对内皮细胞血管生成活性的影响。这将为临床治疗策略奠定坚实的理论基础。薯蓣皂苷通过lncRNA MANTIS调节减轻梗死心脏的心功能障碍。薯蓣皂苷促进MANTIS和BRG 1相互作用，从而促进血管生成和心脏功能恢复。
Dioscin has been widely used in clinics for coronary artery disease (CAD) treatment for years in China. However, the underlying mechanism for Dioscin‐mediated cardioprotective effect has not been elucidated. Here, we showed that Dioscin significantly rescues the cardiac function in mouse model of myocardial infarction (MI), accompanied by the reduction of cardiac fibrosis and apoptosis, resulting from elevated angiogenesis. Mechanistically, Dioscin promotes the proliferation and migration of hypoxic endothelial cells via the up‐regulation of lncRNA MANTIS, which serves as a scaffolding lncRNA within a chromatin remodeling complex. Meanwhile, it enables pol II binding to the transcription start sites, which leads to induced expression of angiogenesis‐related genes, including SOX18, SMAD6, and COUP‐TFII. Conversely, IncRNA MANTIS silencing prevents Dioscin‐induced migration and angiogenesis in hypoxic endothelial cells. Taken together, these data provide new insights that clarifies the cardioprotective effects of Dioscin against myocardial infarcted injury and confirms the effect on angiogenic activity of endothelial cells. This will build a solid theoretical basis for clinical therapeutic strategies. Dioscin alleviates cardiac dysfunction in infarcted hearts via lncRNA MANTIS regulation. Dioscin promotes MANTIS and BRG1 interaction, resulting in angiogenic promotion and cardiac fucntion recovery.
登录
查看更多内容
影响因子：
37.8
作者：
Wu S;Lu Q;Wang Q;Ding Y;Ma Z;Mao X;Huang K;Xie Z;Zou MH
通讯作者：
Zou MH
血管生成因子 AGGF1 激活自噬，在治疗心脏病的血管生成中发挥重要作用
影响因子：
9.8
作者：
Lu Q;Yao Y;Hu Z;Hu C;Song Q;Ye J;Xu C;Wang AZ;Chen Q;Wang QK
通讯作者：
Wang QK
DOI：
10.1038/nrm.2017.104
发表时间：
2018-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Ransohoff JD;Wei Y;Khavari PA
通讯作者：
Khavari PA
影响因子：
7.4
作者：
Tao, Xufeng;Sun, Xiance;Peng, Jinyong
通讯作者：
Peng, Jinyong
影响因子：
37.8
作者：
van Diepen, Sean;Katz, Jason N.;Cohen, Mauricio G.
通讯作者：
Cohen, Mauricio G.