title: 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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Jia
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Clinical Molecular Biology & Central Laboratory, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yanjin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Youfei
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing 100191, China. Electronic address: yangj@bjmu.edu.cn.
authors.forename: Jichun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D021721:Balloon Occlusion; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058472:Receptors, Purinergic P2Y1; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: EP2; FAM3A; P2Y receptor; Proliferation; VSMCs