Long non-coding RNA-SRA promotes neointimal hyperplasia and vascular smooth muscle cells proliferation via MEK-ERK-CREB pathway
Long non-coding RNA-SRA promotes neointimal hyperplasia and vascular smooth muscle cells proliferation via MEK-ERK-CREB pathway
复制标题
长链非编码RNA-SRA通过MEK-ERK-CREB通路促进内膜增生和血管平滑肌细胞增殖
DOI：
10.1016/j.vph.2019.02.005
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发表时间：
2019-05-01
影响因子：
4
通讯作者：
Qin, Li
中科院分区：
文献类型：
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作者：
Zhang, Chan-Juan;Liu, Chan;Qin, Li
长链非编码RNA-类固醇受体RNA激活剂（LncRNA-SRA）是由一类非编码基因转录而来，在调节细胞增殖中发挥着关键作用。然而，lncRNA-SRA 在血管增殖性疾病中的作用仍不清楚。在本研究中，我们在体外过表达lncRNA-SRA，然后研究其生物学后果。采用股动脉钢丝损伤法构建小鼠血管损伤模型。 LncRNA-SRA在受损动脉中过度表达，并显着促进ki67的表达，从而导致新内膜形成总体增加。 LncRNA-SRA 过度表达导致血管平滑肌细胞 (VSMC) 的增殖和迁移。 lncRNA-SRA通过刺激MEK、ERK和CREB（环核苷酸反应元件结合蛋白）的磷酸化促进VSMC增殖。同时，这些作用被 MEK 抑制剂 U0126 阻断。因此，lncRNA-SRA通过激活MEK-ERK-CREB通路促进VSMC增殖。 LncRNA-SRA 可能是以新生内膜增生为特征的血管疾病的一个有前途的治疗靶点。
Long noncoding RNA-steroid receptor RNA activator (LncRNA-SRA) is transcribed from a class of noncoding genes, and plays a critical role in regulating cell proliferation. However, the effect of lncRNA-SRA remains unclear in vascular proliferative diseases. In the present study, we overexpressed lncRNA-SRA in vitro, then investigated the biological consequences. A vascular damage mice model was constructed by performing femoral artery wire injury. LncRNA-SRA was overexpressed in the injured arteries, and significantly promoted the expression of ki67, thereby caused an overall increase in neointima formation. LncRNA-SRA overexpression led to the proliferation and migration of vascular smooth muscle cells (VSMCs). By stimulating the phosphorylation of MEK, ERK and CREB (cyclic nucleotide responsive element binding protein), lncRNA-SRA promoted VSMC proliferation. Meanwhile, these effects were blocked by the MEK inhibitor U0126. Therefore, lncRNA-SRA promoted VSMC proliferation by activating the MEK-ERK-CREB pathway. LncRNA-SRA could be a promising therapeutic target in vascular diseases characterized by neointimal hyperplasia.