当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > 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.

Abstract：

: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.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Jia S,Chen Z,Li J,Chi Y,Wang J,Li S,Luo Y,Geng B,Wang C,Cui Q,Guan Y,Yang J

doi

10.1016/j.yjmcc.2014.05.011

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

173-82

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(14)00172-2

journal_volume

74

pub_type

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