Microrna-26b attenuates monocrotaline-induced pulmonary vascular remodeling via targeting connective tissue growth factor (CTGF) and cyclin D1 (CCND1).
Microrna-26b attenuates monocrotaline-induced pulmonary vascular remodeling via targeting connective tissue growth factor (CTGF) and cyclin D1 (CCND1).
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DOI：
10.18632/oncotarget.10125
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发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Fei G
中科院分区：
文献类型：
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作者：
Wang R;Ding X;Zhou S;Li M;Sun L;Xu X;Fei G
microRNA参与细胞生长的控制，而肺动脉平滑肌细胞增殖失调在肺动脉高压的发展中起着至关重要的作用。本研究的目的是鉴定差异表达的microRNA，并探讨其在疾病治疗中的作用。microRNA表达谱分析显示microRNA-26 b在从野百合碱处理的大鼠中收获的肺动脉平滑肌细胞中差异表达，并且我们验证了microRNA-26 b在体外和体内的靶点CTGF和CCND 1，这两者在我们先前的工作中已经被证明参与肺动脉高压的发病机制。体内实验表明，野百合碱诱导的肺动脉重塑几乎可以完全消除microRNA-26 b的管理，而CTGF或CCND 1的shRNA显着，但只有部分，减弱了重塑沉默设计的目标。此外，microRNA-26 b的外源性表达显著下调人肺动脉平滑肌细胞中的CTGF和CCND 1。microRNA-26 b可能是治疗肺动脉高压的有效工具。
MicroRNAs are involved in the control of cell growth, and deregulated pulmonary artery smooth muscle cell proliferation plays an essential role in the development of pulmonary hypertension. The objective of this study was to identify differentially expressed microRNA(s) and explore its therapeutic role in treatment of the disease. MicroRNA expression profile analysis showed microRNA-26b was differentially expressed in pulmonary artery smooth muscle cells harvested from monocrotaline-treated rats, and we validated microRNA-26b targets, in vitro and in vivo, CTGF and CCND1, both of which have been shown, in our previous work, to be involved in the pathogenesis of pulmonary hypertension. In vivo experiments demonstrated monocrotaline-induced pulmonary artery remodeling could be almost completely abolished by administration of microRNA-26b, while CTGF or CCND1 shRNA significantly, but only partially, attenuated the remodeling by silencing the designed target. Additionally, exogenous expression of the microRNA-26b substantially downregulated CTGF and CCND1 in human pulmonary artery smooth muscle cells. MicroRNA-26b might be a potent therapeutic tool to treat pulmonary hypertension.