LncRNA Tug1 involves in the pulmonary vascular remodeling in mice with hypoxic pulmonary hypertension via the microRNA-374c-mediated Foxc1
LncRNA Tug1 involves in the pulmonary vascular remodeling in mice with hypoxic pulmonary hypertension via the microRNA-374c-mediated Foxc1
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DOI：
10.1016/j.lfs.2019.116769
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发表时间：
2019-11-15
期刊：
影响因子：
6.1
通讯作者：
Meng, Xianguo
中科院分区：
文献类型：
--
作者：
Yang, Lei;Liang, Huan;Meng, Xianguo
低血压性肺动脉高压（HPH）是一种机制复杂的严重肺循环疾病。长链非编码RNA（lncRNA）已被发现参与HPH的发展。本研究旨在探讨lncRNA Tug 1对HPH肺血管重构的影响。建立HPH小鼠模型和HPH肺动脉平滑肌细胞（PASMC）模型（HPH-PASMCs），测定lncRNA Tug 1的表达。然后，评估lncRNA Tug 1、miR-374 c和Foxc 1之间的相互作用。最后，为了研究lncRNA Tug 1对HPH后PASMC活性和肺血管重构的影响，我们在HPH-PASMC和HPH小鼠中沉默lncRNA Tug 1的表达，分别检测PASMC的增殖、凋亡、迁移和小鼠血压。获得的数据显示lncRNA Tug 1在HPH小鼠和HPH-PASMC中高度表达。此外，lncRNA Tug 1通过与miR-374 c结合上调Foxc 1的表达。沉默lncRNA Tug 1可抑制PASMCs的增殖和迁移，但促进PASMCs的凋亡。此外，观察到lncRNA Tug 1沉默通过Foxc 1介导的NOTCH信号通路减轻HPH小鼠的肺血管重塑。同时，lncRNA Tug 1的沉默通过与miR-374 c结合下调Foxc 1的表达，从而抑制PASMCs的增殖和迁移，同时促进PASMCs的凋亡，从而通过Notch信号通路阻止HPH中的肺血管重塑。本研究为治疗HPH提供了新的治疗见解。
Hypoxic pulmonary hypertension (HPH) is a serious and potentially devastating disorder of the pulmonary circulation with complicated mechanisms. Long non-coding RNA (lncRNA) has been revealed to participate in HPH development. This study aimed to explore how lncRNA Tug1 affected the pulmonary vascular remodeling in HPH. A mouse model of HPH and a pulmonary artery smooth muscle cell (PASMC) model of HPH (HPH-PASMCs) were established, where the expression of lncRNA Tug1 was determined. Then, the interaction among lncRNA Tug1, miR-374c, and Foxc1 was assessed. Finally, in order to determine the effects of lncRNA Tug1 on PASMC activities and pulmonary vascular remodeling after HPH, the expression of lncRNA Tug1 was silenced in HPH-PASMCs and HPH mice, with the proliferation, apoptosis, and migration of PASMCs as well as blood pressure in mice measured, respectively. The obtained data revealed that lncRNA Tug1 was highly expressed in HPH mice and HPH-PASMCs. In addition, lncRNA Tug1 up-regulated the expression of Foxc1 by binding to miR-374c. Notably, silencing of lncRNA Tug1 inhibited the proliferation and migration, but promoted the apoptosis of PASMCs. Moreover, lncRNA Tug1 silencing was observed to attenuate the pulmonary vascular remodeling in HPH mice through the Foxc1-mediated NOTCH signaling pathway. Taken conjointly, silencing of lncRNA Tug1 down-regulated the Foxc1 expression by binding to miR-374c, thereby inhibiting the proliferation and migration, while promoting apoptosis of PASMCs to impede pulmonary vascular remodeling in HPH via the Notch signaling pathway. This study provided novel therapeutic insights for treating HPH.