Downregulated PEG3 ameliorates cardiac fibrosis and myocardial injury in mice with ischemia/reperfusion through the NF-κB signaling pathway
Downregulated PEG3 ameliorates cardiac fibrosis and myocardial injury in mice with ischemia/reperfusion through the NF-κB signaling pathway
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下调 PEG3 通过 NF-κB 信号通路改善缺血/再灌注小鼠的心脏纤维化和心肌损伤
DOI：
10.1007/s10863-020-09831-x
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发表时间：
2020-04
影响因子：
3
通讯作者：
Zhigao Li
中科院分区：
文献类型：
--
作者：
Lina Cui;Ying Zhang;Xin Ge;Jie Liu;Xin Zhang;Huiyan Li;Zhigao Li
在新的心脏成体干细胞群中发现了父系表达基因3（PEG 3）的表达，其参与心肌梗死后重构。心肌成纤维细胞在心肌缺血后的修复和重构过程中发挥重要作用，而PEG 3在其中的作用尚不清楚。本研究通过注射p-LV-GFP-sh-PEG 3在缺血/再灌注（I/R）小鼠模型中人工敲除PEG 3，以探讨PEG 3在心脏纤维化、心肌损伤和心肌细胞凋亡中的作用。此外，通过抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）的转导，阐明了核因子κ B（NF-κB）通路的参与。shRNA介导的PEG 3沉默和NF-κB信号通路的抑制均显示出显著减少心肌损伤、梗死面积、减轻心肌重塑和心肌纤维化，沿着抑制心肌细胞凋亡。此外，我们还发现PEG 3沉默可阻断NF-κB信号通路的激活，从而进一步增强PEG 3抑制对I/R损伤的保护作用。这项研究强调了PEG 3沉默通过灭活NF-κB信号通路在预防I/R后心脏纤维化和心肌损伤中的重要性。
Expression of paternally-expressed gene 3 (PEG3) has been identified in new cardiac adult stem cell population, which is involved in post-myocardial infarction remodeling. The cardiac fibroblasts function in the repair and remodeling events after myocardial ischemia, while the role of PEG3 in these events has not been investigated yet. In this study, artificial knockdown of PEG3 through p-LV-GFP-sh-PEG3 injection was performed in a ischemia/reperfusion (I/R) mouse model to explore the role of PEG3 in cardiac fibrosis, myocardial injury and cardiomyocyte apoptosis. Besides, the involvement of nuclear factor kappa B (NF-κB) pathway was illuminated by transduction of inhibitor pyrrolidine dithiocarbamate (PDTC). Both shRNA-mediated silencing of PEG3 and inhibition of the NF-κB signaling pathway were shown to significantly reduce myocardial injury, infarction size, alleviated myocardium remodeling and cardiac fibrosis, along with repressed cardiomyocyte apoptosis. Additionally, we also found that the NF-κB signaling pathway activation was blocked by PEG3 silencing, which could further enhance the protective effects of PEG3 inhibition against I/R induced injury. This study highlights the importance of PEG3 silencing in preventing cardiac fibrosis and myocardial injury after I/R by inactivating the NF-κB signaling pathway.
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DOI：
10.1080/13510002.2017.1416773
发表时间：
2018-12
期刊：
Redox report : communications in free radical research
影响因子：
--
作者：
Beyfuss K;Hood DA
通讯作者：
Hood DA
MICU1 可以防止心肌缺血/再灌注损伤，并通过输入受体 Tom70 对其进行控制。
影响因子：
9
作者：
Xue Q;Pei H;Liu Q;Zhao M;Sun J;Gao E;Ma X;Tao L
通讯作者：
Tao L
影响因子：
5.4
作者：
Jae‐We Cho;K. Lee;Chang-Wook Kim
通讯作者：
Jae‐We Cho;K. Lee;Chang-Wook Kim
DOI：
--
发表时间：
2012
期刊：
--
影响因子：
--
作者：
Silvia Gaspar-Pereira;N. Fullard;P. Townsend;P. Banks;E. Ellis;C. Fox;Aidan Maxwell;L. Murphy;A. Kirk;R. Bauer;J. Caamaño;N. Figg;R. Foo;J. Mann;D. Mann;F. Oakley
通讯作者：
Silvia Gaspar-Pereira;N. Fullard;P. Townsend;P. Banks;E. Ellis;C. Fox;Aidan Maxwell;L. Murphy;A. Kirk;R. Bauer;J. Caamaño;N. Figg;R. Foo;J. Mann;D. Mann;F. Oakley
影响因子：
5.4
作者：
Jae‐We Cho;K. Lee;Chang-Wook Kim
通讯作者：
Jae‐We Cho;K. Lee;Chang-Wook Kim