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On-line Access: 2022-12-15

Received: 2022-03-07

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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.12 P.989-1001


Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3

Author(s):  Zhibiao BAI, Kai HU, Jiahuan YU, Yizhe SHEN, Chun CHEN

Affiliation(s):  First Clinical Medicine Institute, Wenzhou Medical University, Wenzhou 325006, China; more

Corresponding email(s):   chenchunkk@163.com

Key Words:  Macrophage migration inhibitory factor (MIF), Long noncoding RNA (lncRNA), Maternally expressed gene 3 (MEG3), Bone marrow mesenchymal stem cells (BMSCs), β, -Catenin, Apoptosis

Zhibiao BAI, Kai HU, Jiahuan YU, Yizhe SHEN, Chun CHEN. Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3[J]. Journal of Zhejiang University Science B, 2022, 23(12): 989-1001.

@article{title="Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3",
author="Zhibiao BAI, Kai HU, Jiahuan YU, Yizhe SHEN, Chun CHEN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3
%A Zhibiao BAI
%A Kai HU
%A Jiahuan YU
%A Yizhe SHEN
%A Chun CHEN
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 12
%P 989-1001
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200110

T1 - Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3
A1 - Zhibiao BAI
A1 - Kai HU
A1 - Jiahuan YU
A1 - Yizhe SHEN
A1 - Chun CHEN
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 12
SP - 989
EP - 1001
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200110

ObjectiveThis research was performed to explore the effect of macrophage migration inhibitory factor (MIF) on the apoptosis of bone marrow mesenchymal stem cells (BMSCs) in ischemia and hypoxia environments.
MethodsThe cell viability of BMSCs incubated under hypoxia/ischemia (H/I) conditions with or without pretreatment with MIF or triglycidyl isocyanurate (TGIC) was detected using cell counting kit-8 (CCK-8) analysis. Plasmids containing long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) or β;-Catenin small interfering RNA (siRNA) were used to overexpress or downregulate the corresponding gene, and the p53 signaling pathway was activated by pretreatment with TGIC. The influences of MIF, overexpression of lncRNA MEG3, activation of the p53 signaling pathway, and silencing of β;-Catenin on H/I-induced apoptosis of BMSCs were revealed by western blotting, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining.
ResultsFrom the results of CCK-8 assay, western blotting, and flow cytometry, pretreatment with MIF significantly decreased the H/I-induced apoptosis of BMSCs. This effect was inhibited when lncRNA MEG3 was overexpressed by plasmids containing MEG3. The p53 signaling pathway was activated by TGIC, and β;-Catenin was silenced by siRNA. From western blot results, the expression levels of β;-Catenin in the nucleus and phosphorylated p53 (p-p53) were downregulated and upregulated, respectively, when the lncRNA MEG3 was overexpressed. Through flow cytometry, MIF was also shown to significantly alleviate the increased reactive oxygen species (ROS) level of BMSCs caused by H/I.
ConclusionsIn summary, we conclude that MIF protected BMSCs from H/I-induced apoptosis by downregulating the lncRNA MEG3/p53 signaling pathway, activating the Wnt/β;-Catenin signaling pathway, and decreasing ROS levels.

巨噬细胞迁移抑制因子通过调控长链非编码RNA MEG3保护骨髓间充质干细胞免受缺氧/缺血诱导的细胞凋亡

创新点:(1)阐明了长链非编码RNA(lncRNA)MEG3在H/I诱导的小鼠BMSCs凋亡中的作用;(2)发现MIF可以通过调节lncRNA MEG3/p53信号通路缓解H/I介导的BMSCs凋亡;(3)MIF的细胞保护作用还与激活Wnt/β-连环蛋白(β-catenin)信号通路和降低活性氧(ROS)水平相关。
结果:CCK-8、蛋白质印迹法和流式细胞术检测结果显示:MIF预处理可显著降低细胞内的ROS水平,改善H/I诱导的BMSCs凋亡;LncRNA MEG3过表达时细胞核内β-catenin的含量明显减少,而p-p53的表达上调;当p53信号通路被激活,β-catenin的表达被抑制时,MIF对H/I环境下BMSCs的保护作用明显减弱。
结论:MIF通过下调lncRNA MEG3/p53信号通路、激活Wnt/β-catenin信号通路和降低ROS水平来保护BMSCs免受H/I诱导的凋亡。

关键词:巨噬细胞迁移抑制因子;长链非编码RNA MEG3;骨髓间充质干细胞;β-连环蛋白(β-catenin);凋亡

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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