Deletion of MicroRNA-144/451 Cluster Aggravated Brain Injury in Intracerebral Hemorrhage Mice by Targeting 14-3-3ζ

被引：16

作者：

Wang, Xiaohong ^{[1
,2
,3
]}

Hong, Yin ^{[4
]}

Wu, Lei ^{[1
,2
]}

Duan, Xiaochun ^{[5
]}

Hu, Yue ^{[6
]}

Sun, Yongan ^{[7
]}

Wei, Yanqiu ^{[1
]}

Dong, Zhen ^{[1
]}

Wu, Chenghao ^{[1
,2
]}

Yu, Duonan ^{[1
,2
,3
]}

Xu, Jun ^{[8
]}

机构：

[1] Yangzhou Univ, Sch Med, Yangzhou, Jiangsu, Peoples R China

[2] Yangzhou Univ, Jiangsu Key Lab Expt & Translat Noncoding RNA Res, Noncoding RNA Ctr, Yangzhou, Jiangsu, Peoples R China

[3] Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou, Jiangsu, Peoples R China

[4] Capital Med Univ, Beijing Tiantan Hosp, Natl Ctr Clin Res Nervous Syst Dis, Beijing, Peoples R China

[5] Yangzhou Univ, Affiliated Hosp, Dept Neurosurg, Yangzhou, Jiangsu, Peoples R China

[6] Zhangjiagang City First Peoples Hosp, Dept Neurol, Zhangjiagang, Peoples R China

[7] Peking Univ First Hosp, Dept Neurol, Beijing, Peoples R China

[8] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China

来源：

FRONTIERS IN NEUROLOGY | 2021年 / 11卷

关键词：

microRNA-451; intracerebral hemorrhage (ICH); inflammation; 14-3-3; zeta; mice; MIR-451; PROTECTS; MECHANISMS; DEFICITS; STRESS;

D O I：

10.3389/fneur.2020.551411

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

This study aims at evaluating the importance and its underlying mechanism of the cluster of microRNA-144/451 (miR-144/451) in the models with intracerebral hemorrhage (ICH). A model of collagenase-induced mice with ICH and a model of mice with simple miR-144/451 gene knockout (KO) were used in this study. Neurodeficits and the water content of the brain of the mice in each group were detected 3 days after collagenase injection. The secretion of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta), as well as certain biomarkers of oxidative stress, was determined in this study. The results revealed that the expression of miR-451 significantly decreased in the mice with ICH, whereas miR-144 showed no significant changes. KO of the cluster of miR-144/451 exacerbated the neurological deficits and brain edema in the mice with ICH. Further analyses demonstrated that the KO of the cluster of miR-144/451 significantly promoted the secretion of TNF-alpha and IL-1 beta and the oxidative stress in the perihematomal region of the mice with ICH. In addition, the miR-144/451's depletion inhibited the regulatory axis' activities of miR-451-14-3-3 zeta-FoxO3 in the mice with ICH. In conclusion, these data demonstrated that miR-144/451 might protect the mice with ICH against neuroinflammation and oxidative stress by targeting the pathway of miR-451-14-3-3 zeta-FoxO3.

引用

页数：12

共 32 条

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