LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis.
LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis.
复制标题
DOI：
10.1016/j.gendis.2022.04.013
复制
发表时间：
2023-05
期刊：
影响因子：
6.8
通讯作者：
Liao, Junyi
中科院分区：
文献类型：
--
作者：
Du, Chengcheng;Cheng, Qiang;Zhao, Piao;Wang, Claire;Zhu, Zhenglin;Wu, Xiangdong;Gao, Shengqiang;Chen, Bowen;Zou, Jing;Huang, Wei;Liao, Junyi
BMP9介导的MSCs成骨分化机制已被广泛研究，但BMP9诱导血管生成的机制仍需阐明。我们先前研究了Notch1促进BMP9诱导的间充质干细胞(MSCs)成骨-血管生成偶联过程。在这里，我们探讨了LncRNA H19(H19)通过激活Notch1信号来调节BMP9诱导的血管生成的潜在机制。我们发现H19在MSCs中的基础表达水平很高，在体内和体外，沉默H19都能减弱BMP9诱导的MSCs的成骨和血管生成。同时，我们发现BMP9诱导的CD31+细胞的产生是BMP9诱导骨形成所必需的，而沉默H19则显著阻断BMP9诱导的CD31+细胞的产生。此外，我们还发现，在体内，H19的下调抑制了BMP9介导的血管形成和随后的骨形成。从机制上讲，H19通过直接相互作用和磷酸化结合促进P53的磷酸化，P53的磷酸化通过结合Notch1基因的启动子区域而增强Notch1的表达和靶基因的激活。这些结果提示，H19通过促进P53-Notch1血管生成信号轴来调控BMP9诱导的MSCs血管生成。
BMP9 mediated osteogenic differentiation mechanisms of MSCs were widely explored, however, mechanisms of BMP9-induced angiogenesis still need to be clarified. We previously characterized that Notch1 promoted BMP9-induced osteogenesis–angiogenesis coupling process in mesenchymal stem cells (MSCs). Here, we explored the underlying mechanisms of lncRNA H19 (H19) mediated regulation of BMP9-induced angiogenesis through activating Notch1 signaling. We demonstrated that basal expression level of H19 was high in MSCs, and silencing H19 attenuates BMP9-induced osteogenesis and angiogenesis of MSCs both in vitro and in vivo. Meanwhile, we identified that BMP9-induced production of CD31+ cells was indispensable for BMP9-induced bone formation, and silencing H19 dramatically blocked BMP9-induced production of CD31+ cells. In addition, we found that down-regulation of H19 inhibited BMP9 mediated blood vessel formation and followed subsequent bone formation in vivo. Mechanistically, we clarified that H19 promoted p53 phosphorylation by direct interacting and phosphorylating binding, and phosphorylated p53 potentiated Notch1 expression and activation of Notch1 targeting genes by binding on the promoter area of Notch1 gene. These findings suggested that H19 regulated BMP9-induced angiogenesis of MSCs by promoting the p53-Notch1 angiogenic signaling axis.
登录
查看更多内容
影响因子：
3.7
作者：
Deng F;Chen X;Liao Z;Yan Z;Wang Z;Deng Y;Zhang Q;Zhang Z;Ye J;Qiao M;Li R;Denduluri S;Wang J;Wei Q;Li M;Geng N;Zhao L;Zhou G;Zhang P;Luu HH;Haydon RC;Reid RR;Yang T;He TC
通讯作者：
He TC
影响因子：
14
作者：
Ho-Shui-Ling A;Bolander J;Rustom LE;Johnson AW;Luyten FP;Picart C
通讯作者：
Picart C
影响因子：
12.4
作者：
Kim, S. B.;Chae, G. W.;Joe, C. O.
通讯作者：
Joe, C. O.
影响因子：
5.5
作者：
Dai, Guangming;Xiao, Haozhuo;Huang, Wei
通讯作者：
Huang, Wei
影响因子：
21.3
作者：
通讯作者：
--