Smooth muscle-specific HuR knockout induces defective autophagy and atherosclerosis.
Smooth muscle-specific HuR knockout induces defective autophagy and atherosclerosis.
复制标题
平滑肌特异性 HuR 敲除会诱导自噬缺陷和动脉粥样硬化。
DOI：
10.1038/s41419-021-03671-2
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发表时间：
2021-04-09
影响因子：
9
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Liu S;Jiang X;Cui X;Wang J;Liu S;Li H;Yang J;Zhang C;Zhang W
Human antigen R (HuR) is a widespread RNA-binding protein involved in homeostatic regulation and pathological processes in many diseases. Atherosclerosis is the leading cause of cardiovascular disease and acute cardiovascular events. However, the role of HuR in atherosclerosis remains unknown. In this study, mice with smooth muscle-specific HuR knockout (HuRSMKO) were generated to investigate the role of HuR in atherosclerosis. HuR expression was reduced in atherosclerotic plaques. As compared with controls, HuRSMKO mice showed increased plaque burden in the atherosclerotic model. Mechanically, HuR could bind to the mRNAs of adenosine 5′-monophosphate-activated protein kinase (AMPK) α1 and AMPKα2, thus increasing their stability and translation. HuR deficiency reduced p-AMPK and LC3II levels and increased p62 level, thereby resulting in defective autophagy. Finally, pharmacological AMPK activation induced autophagy and suppressed atherosclerosis in HuRSMKO mice. Our findings suggest that smooth muscle HuR has a protective effect against atherosclerosis by increasing AMPK-mediated autophagy.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
20.1
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G
DOI：
10.1158/1541-7786.mcr-16-0361
发表时间：
2017-06
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Lal S;Cheung EC;Zarei M;Preet R;Chand SN;Mambelli-Lisboa NC;Romeo C;Stout MC;Londin E;Goetz A;Lowder CY;Nevler A;Yeo CJ;Campbell PM;Winter JM;Dixon DA;Brody JR
通讯作者：
Brody JR
影响因子：
4
作者：
Gantt, Kira R.;Cherry, Joy;Pekala, Phillip H.
通讯作者：
Pekala, Phillip H.
影响因子：
13.3
作者：
Liu, Kun;Zhao, Enpeng;Czaja, Mark J.
通讯作者：
Czaja, Mark J.