CD9 induces cellular senescence and aggravates atherosclerotic plaque formation

被引：51
作者：
Cho, Jung Hee [1 ,2 ,3 ]
Kim, Eok-Cheon [1 ,2 ]
Son, Youlim [1 ,2 ]
Lee, Da-Woon [1 ,2 ]
Park, Yong Seop [1 ,2 ]
Choi, Joon Hyuk [4 ]
Cho, Kyung-Hyun [5 ]
Kwon, Ki-Sun [6 ]
Kim, Jae-Ryong [1 ,2 ]
机构：
[1] Yeungnam Univ, Dept Biochem & Mol Biol, Daegu 42415, South Korea
[2] Yeungnam Univ, Smart Aging Convergence Res Ctr, Daegu 42415, South Korea
[3] Korea Res Inst Biosci & Biotechnol, Personalized Genom Med Res Ctr, Daejeon 34141, South Korea
[4] Yeungnam Univ, Coll Med, Dept Pathol, Daegu 42415, South Korea
[5] Yeungnam Univ, Sch Biotechnol, Gyongsan 38541, South Korea
[6] Korea Res Inst Biosci & Biotechnol, Aging Res Ctr, Daejeon 34141, South Korea
来源：
CELL DEATH AND DIFFERENTIATION | 2020年 / 27卷 / 09期
基金：
新加坡国家研究基金会;
关键词：
HIGH-DENSITY-LIPOPROTEIN; TETRASPANIN CD9; REPLICATIVE SENESCENCE; GROWTH-FACTOR; ENDOTHELIAL-CELLS; A-I; ROLES; P53; P110-ALPHA; PI3K;
D O I：
10.1038/s41418-020-0537-9
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
CD9, a 24 kDa tetraspanin membrane protein, is known to regulate cell adhesion and migration, cancer progression and metastasis, immune and allergic responses, and viral infection. CD9 is upregulated in senescent endothelial cells, neointima hyperplasia, and atherosclerotic plaques. However, its role in cellular senescence and atherosclerosis remains undefined. We investigated the potential mechanism for CD9-mediated cellular senescence and its role in atherosclerotic plaque formation. CD9 knockdown in senescent human umbilical vein endothelial cells significantly rescued senescence phenotypes, while CD9 upregulation in young cells accelerated senescence. CD9 regulated cellular senescence through a phosphatidylinositide 3 kinase-AKT-mTOR-p53 signal pathway. CD9 expression increased in arterial tissues from humans and rats with age, and in atherosclerotic plaques in humans and mice. Anti-mouse CD9 antibody noticeably prevented the formation of atherosclerotic lesions in ApoE(-/-) mice and Ldlr(-/-) mice. Furthermore, CD9 ablation in ApoE(-/-) mice decreased atherosclerotic lesions in aorta and aortic sinus. These results suggest that CD9 plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that CD9 is a novel target for prevention and treatment of vascular aging and atherosclerosis.
引用
收藏
页码：2681 / 2696
页数：16
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