School of Public Health, North China University of Science and Technology, PR China.
School of Public Health, North China University of Science and Technology, PR China.
Life Sci. 2020 Dec 1;262:118491. doi: 10.1016/j.lfs.2020.118491. Epub 2020 Oct 1.
Aurora kinase A (AURKA) is a mitotic serine/threonine kinase that contributes to the regulation of cell-cycle progression. AURKA has been shown to further enhance Wnt/β-catenin signaling; however, in the context of driving aortic-dissecting aneurysm (ADA), the molecular details of this phenomenon remain poorly understood.
A total of 43 specimens of ADA tissues and eleven healthy aortic tissues as controls were collected from the hospital. Pathological changes were observed by hematoxylin and eosin staining. AURKA expression in aortic tissues was detected by real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry staining. The proliferative and migratory effects of AURKA were observed in cultured vascular smooth muscle cells (VSMCs).
AURKA expression was significantly increased in aorta samples from ADA patients relative to those from normal donors, and the expression was even higher in ruptured ADA tissues. AURKA overexpression promoted and AURKA knockdown inhibited, respectively, the proliferation, and migration of VSMCs. Angiotensin II (AngII) treatment of VSMCs significantly increased AURKA expression. The knockdown of AURKA partially reversed AngII-induced VSMC proliferation and migration. Finally, the downregulation of AURKA inhibited cell proliferation by inactivating the p-GSK-3β/β-catenin pathway.
The GSK-3β/β-catenin signaling pathway participates in the AURKA-regulated proliferation and migration of VSMCs. The expression of AURKA may be involved in the phenotypic conversion of VSMC and the occurrence and development of ADA and could be a potential molecular target for ADA therapy.
极光激酶 A（AURKA）是一种有丝分裂丝氨酸/苏氨酸激酶，有助于调节细胞周期进程。已经表明 AURKA 进一步增强了 Wnt/β-catenin 信号；然而，在驱动主动脉夹层动脉瘤（ADA）的情况下，这种现象的分子细节仍知之甚少。
从医院共收集了 43 份 ADA 组织标本和 11 份健康主动脉组织作为对照。通过苏木精和伊红染色观察病理变化。通过实时定量聚合酶链反应（RT-qPCR）、western blot 和免疫组织化学染色检测主动脉组织中 AURKA 的表达。观察 AURKA 在培养的血管平滑肌细胞（VSMCs）中的增殖和迁移作用。
ADA 患者的主动脉样本中 AURKA 的表达明显高于正常供体，破裂的 ADA 组织中的表达甚至更高。AURKA 过表达促进和 AURKA 敲低分别抑制了 VSMCs 的增殖和迁移。血管紧张素 II（AngII）处理 VSMCs 显著增加了 AURKA 的表达。AURKA 的敲低部分逆转了 AngII 诱导的 VSMC 增殖和迁移。最后，AURKA 的下调通过失活 p-GSK-3β/β-catenin 通路抑制了细胞增殖。
GSK-3β/β-catenin 信号通路参与了 AURKA 调节的 VSMCs 增殖和迁移。AURKA 的表达可能参与了 VSMC 的表型转化以及 ADA 的发生和发展，并且可能是 ADA 治疗的潜在分子靶标。
