Jia Meng1, He-Liang Liu1, Dong Ma1, Hong-Yan Wang1, Yue Peng1, Hong-Li Wang2. 1. School of Public Health, North China University of Science and Technology, PR China. 2. School of Public Health, North China University of Science and Technology, PR China. Electronic address: whllhl@163.com.
Abstract
AIMS: 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. MATERIALS AND METHODS: 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). KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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. MATERIALS AND METHODS: 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). KEY FINDINGS:AURKA expression was significantly increased in aorta samples from ADApatients 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. SIGNIFICANCE: 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.