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首页> 外文期刊>Journal of Molecular and Cellular Cardiology >FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury
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FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury

机译:FAM3A促进血管平滑肌细胞增殖和迁移,并加剧球囊损伤后大鼠动脉的新内膜形成

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The biological function of FAM3A, the first member of family with sequence similarity 3 (FAM3) gene family, remains largely unknown. This study aimed to determine its role in the proliferation and migration of vascular smooth muscle cells (VSMCs). Immunohistochemical staining revealed that FAM3A protein is expressed in the tunica media of rodent arteries, and its expression is reduced with an increase in prostaglandin E receptor 2 (EP2) expression after injury. In vitro, FAM3A overexpression promotes proliferation and migration of VSMCs, whereas FAM3A silencing inhibits these processes. In vivo, FAM3A overexpression results in exaggerated neointima formation of rat carotid artery after balloon injury. FAM3A activates Akt in a PI3K-dependent manner. In contrast, FAM3A induces ERK1/2 activation independent of PI3K. FAM3A protein is subcellularly located in mitochondria, where it affects ATP production and release. Activation of EP2 represses FAM3A expression, leading to impaired ATP production and release in VSMCs. FAM3A-induced activation of Akt and ERK1/2 pathways, proliferation and migration of VSMCs are inhibited by P2 receptor antagonist suramin. Furthermore, inhibition or knockdown of P2Y1 receptor inihibits FAM3A-induced proliferation and migration of VSMCs. In conclusion, FAM3A promotes proliferation and migration of VSMCs via P2Y1 receptor-mediated activation of Akt and ERK1/2 pathways. In injured vessels, FAM3A was repressed by upregulated EP2 expression, leading to the attenuation of ATP-P2Y1 receptor signaling, which is beneficial for preventing excessive proliferation and migration of VSMCs.
机译:FAM3A,具有序列相似性3(FAM3)基因家族的第一个成员的生物学功能仍然是未知的。这项研究旨在确定其在血管平滑肌细胞(VSMC)增殖和迁移中的作用。免疫组织化学染色显示,FAM3A蛋白在啮齿动物的动脉膜中表达,并且随着损伤后前列腺素E受体2(EP2)表达的增加而降低。在体外,FAM3A过表达促进VSMC的增殖和迁移,而FAM3A沉默则抑制这些过程。在体内,FAM3A过表达导致球囊损伤后大鼠颈动脉的新内膜过度形成。 FAM3A以PI3K依赖的方式激活Akt。相反,FAM3A诱导独立于PI3K的ERK1 / 2激活。 FAM3A蛋白位于线粒体的亚细胞中,在此处影响ATP的产生和释放。 EP2的激活会抑制FAM3A表达,从而导致VSMC中ATP的产生和释放受损。 P2受体拮抗剂苏拉明抑制FAM3A诱导的Akt和ERK1 / 2途径活化,VSMC增殖和迁移。此外,抑制或敲低P2Y1受体抑制FAM3A诱导的VSMC增殖和迁移。总之,FAM3A通过P2Y1受体介导的Akt和ERK1 / 2途径的激活促进VSMC的增殖和迁移。在受伤的血管中,FAM3A被上调的EP2表达抑制,导致ATP-P2Y1受体信号转导减弱,这对于防止VSMC过度增殖和迁移是有益的。

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