MicroRNA-223-3p Protect Against Radiation-Induced Cardiac Toxicity by Alleviating Myocardial Oxidative Stress and Programmed Cell Death via Targeting the AMPK Pathway

被引:11
|
作者
Zhang, Dao-ming [1 ]
Deng, Jun-jian [1 ]
Wu, Yao-gui [1 ]
Tang, Tian [1 ]
Xiong, Lin [2 ]
Zheng, Yong-fa [1 ]
Xu, Xi-ming [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Canc Ctr, Wuhan, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Dept Pathol, Wuhan, Peoples R China
基金
中国国家自然科学基金;
关键词
RIHD; MiR-223-3p; apoptosis; oxidative stress; AMPK; IONIZING-RADIATION; HEART; APOPTOSIS; MITOCHONDRIA; INFARCTION; MECHANISM; SURVIVAL; INJURY; REPAIR; LENS;
D O I
10.3389/fcell.2021.801661
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objectives: Radiotherapy improves the survival rate of cancer patients, yet it also involves some inevitable complications. Radiation-induced heart disease (RIHD) is one of the most serious complications, especially the radiotherapy of thoracic tumors, which is characterized by cardiac oxidative stress disorder and programmed cell death. At present, there is no effective treatment strategy for RIHD; in addition, it cannot be reversed when it progresses. This study aims to explore the role and potential mechanism of microRNA-223-3p (miR-223-3p) in RIHD.Methods: Mice were injected with miR-223-3p mimic, inhibitor, or their respective controls in the tail vein and received a single dose of 20 Gy whole-heart irradiation (WHI) for 16 weeks after 3 days to construct a RIHD mouse model. To inhibit adenosine monophosphate activated protein kinase (AMPK) or phosphodiesterase 4D (PDE4D), compound C (CompC) and AAV9-shPDE4D were used.Results: WHI treatment significantly inhibited the expression of miR-223-3p in the hearts; furthermore, the levels of miR-223-3p decreased in a radiation time-dependent manner. miR-223-3p mimic significantly relieved, while miR-223-3p inhibitor aggravated apoptosis, oxidative damage, and cardiac dysfunction in RIHD mice. In addition, we found that miR-223-3p mimic improves WHI-induced myocardial injury by activating AMPK and that the inhibition of AMPK by CompC completely blocks these protective effects of miR-223-3p mimic. Further studies found that miR-223-3p lowers the protein levels of PDE4D and inhibiting PDE4D by AAV9-shPDE4D blocks the WHI-induced myocardial injury mediated by miR-223-3p inhibitor.Conclusion: miR-223-3p ameliorates WHI-induced RIHD through anti-oxidant and anti-programmed cell death mechanisms via activating AMPK by PDE4D regulation. miR-223-3p mimic exhibits potential value in the treatment of RIHD.
引用
收藏
页数:12
相关论文
共 7 条
  • [1] Huc-MSCs protect porcine islets from hypoxia-induced cell death via alleviating oxidative stress and enhancing the ERK pathway
    Tan, Y.
    Nie, W.
    Chen, C.
    Rong, P.
    Wang, W.
    EUROPEAN JOURNAL OF IMMUNOLOGY, 2019, 49 : 1506 - 1506
  • [2] Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway
    Wang, Xue-jun
    Zhang, Dan
    Yang, Yan-ting
    Li, Xiao-ying
    Li, Hong-na
    Zhang, Xiao-peng
    Long, Jun-yi
    Lu, Yun-qiong
    Liu, Li
    Yang, Guang
    Liu, Jie
    Hong, Jue
    Wu, Huan-gan
    Ma, Xiao-peng
    FRONTIERS IN IMMUNOLOGY, 2023, 14
  • [3] MicroRNA-15a-5p plays a role in osteogenic MC3T3-E1 cells differentiation by targeting PDCD4 (programmed cell death 4) via Wnt/β-catenin dependent signaling pathway
    Wang, Qiang
    Miao, Yiming
    Qian, Zhiyuan
    Chen, Lidong
    Lu, Tong
    Xu, Yue
    Jiang, Xiaowei
    Shen, Yingchao
    BIOENGINEERED, 2021, 12 (01) : 8173 - 8185
  • [4] MiR-183-5p Enhances Autophagy by Targeting IRS1/PI3K-Oxidative Stress Signaling Pathway via Affecting Sepsis-Induced Cardiac Dysfunction
    Dong, Qinzuo
    Liu, Lanlan
    Li, Yuejin
    Yang, Jun
    Li, Lingling
    Zhao, Rong
    Li, Xiang
    Luan, Yunpeng
    LATIN AMERICAN JOURNAL OF PHARMACY, 2023, 42 (07): : 1460 - 1470
  • [5] MicroRNA-129-1-3p attenuates autophagy-dependent cell death by targeting MCU in granulosa cells of laying hens under H2O2-induced oxidative stress
    Zhu, Mingkun
    Yan, Ming
    Chen, Jianfei
    Li, Huaiyu
    Zhang, Yeshun
    POULTRY SCIENCE, 2023, 102 (10)
  • [6] Atorvastatin-pretreated mesenchymal stem cell-derived extracellular vesicles promote cardiac repair after myocardial infarction via shifting macrophage polarization by targeting microRNA-139-3p/Stat1 pathway
    Yu Ning
    Peisen Huang
    Guihao Chen
    Yuyan Xiong
    Zhaoting Gong
    Chunxiao Wu
    Junyan Xu
    Wenyang Jiang
    Xiaosong Li
    Ruijie Tang
    Lili Zhang
    Mengjin Hu
    Jing Xu
    Jun Xu
    Haiyan Qian
    Chen Jin
    Yuejin Yang
    BMC Medicine, 21
  • [7] Atorvastatin-pretreated mesenchymal stem cell-derived extracellular vesicles promote cardiac repair after myocardial infarction via shifting macrophage polarization by targeting microRNA-139-3p/Stat1 pathway
    Ning, Yu
    Huang, Peisen
    Chen, Guihao
    Xiong, Yuyan
    Gong, Zhaoting
    Wu, Chunxiao
    Xu, Junyan
    Jiang, Wenyang
    Li, Xiaosong
    Tang, Ruijie
    Zhang, Lili
    Hu, Mengjin
    Xu, Jing
    Xu, Jun
    Qian, Haiyan
    Jin, Chen
    Yang, Yuejin
    BMC MEDICINE, 2023, 21 (01)