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Inhibitory effect of microRNA-762 on pyroptotic cell death of mesenchymal stem cell after transplantation in ischemic heart

Other Titles
 허혈성 심장에 이식된 중간엽 줄기세포의 파이롭토시스 세포사멸에 대한 microRNA-762의 억제효과 
Authors
 이창연 
Issue Date
2018
Description
융합오믹스의생명과학
Abstract
The high death rate of cells transplanted into damaged hearts due to exposure to harsh conditions, such as hypoxia and high reactive oxygen species (ROS) concentrations, hampers the efficacy of stem cell-based therapy. Preventing cell death after transplantation is an essential requirement for using cell therapy to treat damaged hearts. Thus, the long-term survival of transplanted cells is a major goal in optimizing cell therapeutic applications. In addition to necrosis, apoptosis, and anoikis, pyroptosis has recently been recognized as a form of programmed cell death in the myocardium. Pyroptosis is mediated by cell lysis and the release of inflammatory cytokines, such as interleukin (IL)-1β and IL-18. Furthermore, cysteine-dependent aspartate-specific proteases 1 (caspases 1) are sequentially cleaved by pyroptosis-mediated cell death. Suppressing pyroptosis to improve transplanted stem cell survival in the infarcted myocardium has not been well studied. Thus, we inhibited pyroptosis to increase the survival rate of transplanted cells in the damaged myocardium. In the present study, IL-1β staining demonstrated that pyroptosis occurred in hearts with ischemia-reperfusion (I/R) injury. In addition, the expression of F4/80, a specific macrophage marker, was increased in the damaged myocardium, thus indicating macrophage recruitment. Next, increased pyroptosis-specific gene expression levels were found in RAW264.7 cells treated with lipopolysaccharides (LPS) and interferon (IFN)-γ. These data show that M1 macrophages are specifically involved in pyroptosis in hearts with I/R injury. Furthermore, specific microRNAs (miRs) have been identified to inhibit pyroptosis as well as improve the survival of stem cells transplanted into damaged hearts. miRs were screened by differentially expressed gene (DEG) analysis, and miRNA-762, which inhibits IL-1β expression by binding to its 3’ untranslated region (UTR), was identified. Significantly decreased pyroptosis-related gene and protein expression levels were detected in mesenchymal stem cells (MSCs) transfected with miR-762. Finally, cardiac fibrosis was ameliorated by transplanting miR-762-transfected MSCs into hearts with I/R injury. In conclusion, pyroptosis is an essential mechanism that induces inflammation and cell death. In addition, inhibiting the pyroptosis factor IL-1β by transfecting miR-762 into MSCs could be used in cell therapy for treating damaged hearts.
Files in This Item:
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Appears in Collections:
7. Others (기타) > Others (기타) > 5. Others
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166377
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