FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury
FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury
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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中新内膜的形成。
DOI：
10.1016/j.yjmcc.2014.05.011
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发表时间：
2014-09-01
影响因子：
5
通讯作者：
Yang, Jichun
中科院分区：
文献类型：
--
作者：
Jia, Shi;Chen, Zhenzhen;Yang, Jichun
FAM 3A基因是FAM 3基因家族的第一个成员，其生物学功能尚不清楚。本研究旨在确定其在血管平滑肌细胞（VSMCs）增殖和迁移中的作用。免疫组织化学染色显示，FAM 3A蛋白在啮齿动物动脉的图尼卡中膜中表达，并且其表达随着损伤后前列腺素E受体2（EP 2）表达的增加而减少。在体外，FAM 3A过表达促进VSMCs的增殖和迁移，而FAM 3A沉默抑制这些过程。在体内，FAM 3A过表达导致大鼠颈动脉球囊损伤后过度的新生内膜形成。FAM 3A以PI 3 K依赖性方式激活Akt。相反，FAM 3A诱导ERK 1/2激活，而不依赖于PI 3 K。FAM 3A蛋白位于线粒体的亚细胞内，影响ATP的产生和释放。EP 2的激活抑制FAM 3A的表达，导致VSMC中ATP的产生和释放受损。P2受体拮抗剂苏拉明可抑制FAM 3A诱导的Akt和ERK 1/2通路的激活以及VSMCs的增殖和迁移。此外，抑制或敲低P2 Y1受体可抑制FAM 3A诱导的VSMCs增殖和迁移。总之，FAM 3A通过P2 Y1受体介导的Akt和ERK 1/2通路的激活促进VSMCs的增殖和迁移。在损伤血管中，FAM 3A被上调的EP 2表达所抑制，导致ATP-P2 Y1受体信号转导减弱，这有利于防止VSMCs过度增殖和迁移。(C)2014爱思唯尔有限公司版权所有。
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. (C) 2014 Elsevier Ltd. All rights reserved.