Abstract
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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The authors want to show their appreciation to the colleagues for their helpful suggestions and technical assistance.
Funding
This study was supported by National Natural Science Foundation of China (General Program) (No. 81872157) and Haiyan Fund of Harbin Medical University Cancer Hospital (No. JJZD2016-05).
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Animal treatment in this study was conducted under approval of the Animal Experimentation Ethics Committee of Harbin Medical University Cancer Hospital, which was in strict accordance with the recommendations of animal ethical standard.
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Cui, L., Zhang, Y., Ge, X. et al. Downregulated PEG3 ameliorates cardiac fibrosis and myocardial injury in mice with ischemia/reperfusion through the NF-κB signaling pathway. J Bioenerg Biomembr 52, 143–154 (2020). https://doi.org/10.1007/s10863-020-09831-x
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DOI: https://doi.org/10.1007/s10863-020-09831-x