PDF(Pubmed)
Abstract：
BACKGROUND: ( -)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol isolated from green tea, has recently garnered attention for its potential protective role against acute myocardial infarction (MI) via inhibiting inflammation. Herein, we tested whether EGCG participates in modulating cardiac ischemia reperfusion-induced injury and elucidate its potential mechanisms.
METHODS: To induce MI in mice, we employed coronary artery ligation, while cell models utilized oxygen glucose deprivation/re-oxygenation (OGD/R)-treated HL-1 cells. TTC, HE and Massion staining evaluated the pathological changes of heart tissues. Besides, RNA-pull down and RIP assays analyzed the interactions of MEG3/TAF15 and AIM2 mRNA/TAF15. FISH associated with immunofiuorescence (IF) double staining was conducted to measure the co-localization of MEG3 and TAF15.
RESULTS: In vitro and in vivo evidence supported that EGCG treatment improved cardiomyocytes viability while inhibiting the expressions of AIM2, C-caspase-1, ASC, GSDMD-N, IL-18 and IL-1β. Knockdown of MEG3 intensified EGCG\'s therapeutic effects both in vitro and in vivo. LncRNA MEG3 and AIM2 mRNA interacted with TAF15, and MEG3, in turn, promoted the stability of AIM2 mRNA through regulating TAF15. Overexpression of TAF15 reversed the promoting effect of EGCG and MEG3 knockdown on cell viability, and the inhibiting effect on cell pyroptosis.
CONCLUSIONS: EGCG protected cardiomyocytes from pyroptosis by the MEG3/TAF15/AIM2 axis, indicating EGCG as a potential novel therapeutic strategy for managing MI.
METHODS: To induce MI in mice, we employed coronary artery ligation, while cell models utilized oxygen glucose deprivation/re-oxygenation (OGD/R)-treated HL-1 cells. TTC, HE and Massion staining evaluated the pathological changes of heart tissues. Besides, RNA-pull down and RIP assays analyzed the interactions of MEG3/TAF15 and AIM2 mRNA/TAF15. FISH associated with immunofiuorescence (IF) double staining was conducted to measure the co-localization of MEG3 and TAF15.
RESULTS: In vitro and in vivo evidence supported that EGCG treatment improved cardiomyocytes viability while inhibiting the expressions of AIM2, C-caspase-1, ASC, GSDMD-N, IL-18 and IL-1β. Knockdown of MEG3 intensified EGCG\'s therapeutic effects both in vitro and in vivo. LncRNA MEG3 and AIM2 mRNA interacted with TAF15, and MEG3, in turn, promoted the stability of AIM2 mRNA through regulating TAF15. Overexpression of TAF15 reversed the promoting effect of EGCG and MEG3 knockdown on cell viability, and the inhibiting effect on cell pyroptosis.
CONCLUSIONS: EGCG protected cardiomyocytes from pyroptosis by the MEG3/TAF15/AIM2 axis, indicating EGCG as a potential novel therapeutic strategy for managing MI.
摘要：
背景：（-）-表没食子儿茶素-3-没食子酸酯（EGCG），一种从绿茶中分离出的生物活性多酚，最近因其通过抑制炎症对急性心肌梗死（MI）的潜在保护作用而引起了关注。在这里，我们测试了EGCG是否参与调节心肌缺血再灌注损伤,并阐明了其潜在机制.
方法：在小鼠中诱导MI，我们做了冠状动脉结扎术,而细胞模型利用氧葡萄糖剥夺/复氧（OGD/R）处理的HL-1细胞。TTC,HE和Massion染色评价心脏组织的病理变化。此外,RNA下拉和RIP测定分析了MEG3/TAF15和AIM2mRNA/TAF15的相互作用。进行与免疫荧光（IF）双重染色相关的FISH以测量MEG3和TAF15的共定位。
结果：体外和体内证据支持EGCG治疗改善心肌细胞活力，同时抑制AIM2，C-caspase-1，ASC，GSDMD-N,IL-18和IL-1β。MEG3的敲除增强了EGCG的体外和体内治疗效果。LncRNAMEG3和AIM2mRNA依次与TAF15和MEG3相互作用，通过调节TAF15促进AIM2mRNA的稳定性。TAF15的过表达逆转了EGCG和MEG3敲低对细胞活力的促进作用，以及对细胞焦亡的抑制作用。
结论：EGCG通过MEG3/TAF15/AIM2轴保护心肌细胞免于焦亡，表明EGCG是管理MI的潜在新治疗策略。
方法：在小鼠中诱导MI，我们做了冠状动脉结扎术,而细胞模型利用氧葡萄糖剥夺/复氧（OGD/R）处理的HL-1细胞。TTC,HE和Massion染色评价心脏组织的病理变化。此外,RNA下拉和RIP测定分析了MEG3/TAF15和AIM2mRNA/TAF15的相互作用。进行与免疫荧光（IF）双重染色相关的FISH以测量MEG3和TAF15的共定位。
结果：体外和体内证据支持EGCG治疗改善心肌细胞活力，同时抑制AIM2，C-caspase-1，ASC，GSDMD-N,IL-18和IL-1β。MEG3的敲除增强了EGCG的体外和体内治疗效果。LncRNAMEG3和AIM2mRNA依次与TAF15和MEG3相互作用，通过调节TAF15促进AIM2mRNA的稳定性。TAF15的过表达逆转了EGCG和MEG3敲低对细胞活力的促进作用，以及对细胞焦亡的抑制作用。
结论：EGCG通过MEG3/TAF15/AIM2轴保护心肌细胞免于焦亡，表明EGCG是管理MI的潜在新治疗策略。
