Histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit exacerbates inflammation in depression rats by modulating microglia polarization.
Histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit exacerbates inflammation in depression rats by modulating microglia polarization.
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DOI：
10.1080/21655979.2022.2036892
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发表时间：
2022-03
期刊：
影响因子：
4.9
通讯作者：
Lei S
中科院分区：
文献类型：
--
作者：
Huang X;Yang Q;Xie L;Lei S
抑郁症是情绪痛苦和生活质量下降的主要原因。zeste 2多梳抑制复合体2亚基增强子（EZH2）参与人类疾病组蛋白甲基化。本实验旨在探讨EZH2对抑郁症的作用机制。通过慢性不可预测轻度应激（CUMS）治疗，建立抑郁大鼠模型，鉴定大鼠抑郁样行为。测定EZH2的表达，然后沉默，以评估其对抑郁样行为和神经炎症的影响。分离、培养、鉴定和激活小胶质细胞以评估EZH2的表达。观察EZH2对小胶质细胞极化的影响。接下来，分析了microRNA (miR)-29b-3p与EZH2或基质金属肽酶2 （MMP2）的结合关系。检测miR-29b-3p表达水平和MMP2转录水平。此外，我们还测试了miR-29b-3p在小胶质细胞极化中的作用。CUMS诱导后出现抑郁样行为。EZH2在cums处理大鼠和脂多糖（LPS）诱导的小胶质细胞中过表达。EZH2沉默逆转了抑郁样行为。EZH2沉默通过操纵小胶质细胞m2型极化减轻抑郁症的炎症。EZH2靶向miR-29b-3p表达，促进MMP2转录。抑制miR-29b-3p逆转了EZH2沉默在小胶质细胞m2型极化中的作用，并促进了炎症。EZH2通过结合miR-29b-3p启动子和组蛋白h3 -赖氨酸27-三甲基化上调三甲基化抑制miR-29b-3p的表达，进而升高MMP2转录，引发小胶质细胞m1型极化，从而加重抑郁样行为和抑郁症的神经炎症。
Depression is a major cause of emotional agony and degraded living quality. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is involved in histone methylation in human diseases. This experiment was designed to investigate the mechanism of EZH2 on depression. Depression rat model was established via the treatment of chronic unpredictable mild stress (CUMS) to identify rat depression-like behaviors. EZH2 expression was determined and then silenced to assess its effect on depression-like behaviors and neuroinflammation. Microglia were isolated, cultured, identified and activated to assess EZH2 expression. Effect of EZH2 on microglia polarization was evaluated. Next, the binding relation between microRNA (miR)-29b-3p and EZH2 or matrix metallopeptidase 2 (MMP2) was analyzed. Levels of miR-29b-3p expression and MMP2 transcription were examined. Additionally, the role of miR-29b-3p in microglia polarization was tested. Depression-like behaviors were exhibited after CUMS induction. EZH2 was overexpressed in CUMS-treated rats and lipopolysaccharide (LPS)-induced microglia. EZH2 silencing reversed depression-like behaviors. EZH2 silencing mitigated inflammation in depression by manipulating microglia M2-type polarization. EZH2 targeted miR-29b-3p expression to promote MMP2 transcription. Inhibition of miR-29b-3p reversed the role of EZH2 silencing in microglia M2-type polarization and promoted inflammation. EZH2 inhibited miR-29b-3p expression by combining with miR-29b-3p promoter and trimethylation of histone H3-lysine 27-trimethylated upregulation, and then elevated MMP2 transcription and triggered microglia M1-type polarization, thus exacerbating depression-like behaviors and neuroinflammation of depression.
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DOI：
10.1146/annurev-clinpsy-050817-084811
发表时间：
2018-01-01
期刊：
ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 14
影响因子：
--
作者：
Hammen, Constance
通讯作者：
Hammen, Constance
影响因子：
4
作者：
Hong, Feng;Zhao, Mengxue;Feng, Linyin
通讯作者：
Feng, Linyin
影响因子：
6.1
作者：
Guo, Yuanxin;Gan, Xiaohong;Tang, Hongmei
通讯作者：
Tang, Hongmei
影响因子：
5.3
作者：
Brites D;Fernandes A
通讯作者：
Fernandes A
影响因子：
4
作者：
Chen, Fei;Lu, Jingchao;Cui, Wei
通讯作者：
Cui, Wei