Abstract：
BACKGROUND: With an increasing number of myocardial infarction (MI) patients, myocardial fibrosis is becoming a widespread health concern. It\'s becoming more and more urgent to conduct additional research and investigations into efficient treatments. Ethyl ferulate (EF) is a naturally occurring substance with cardioprotective properties. However, the extent of its impact and the underlying mechanism of its treatment for myocardial fibrosis after MI remain unknown.
OBJECTIVE: The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI.
METHODS: Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2\'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF.
RESULTS: In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-β1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice.
CONCLUSIONS: EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.
OBJECTIVE: The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI.
METHODS: Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2\'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF.
RESULTS: In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-β1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice.
CONCLUSIONS: EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.
摘要：
背景：随着心肌梗死（MI）患者数量的增加，心肌纤维化正成为人们广泛关注的健康问题。对有效的治疗方法进行更多的研究和调查变得越来越紧迫。阿魏酸乙酯(EF)是具有心脏保护特性的天然存在的物质。然而,其对MI后心肌纤维化的影响程度和治疗机制尚不清楚.
目的：本研究的目的是探讨EF如何影响MI后心肌纤维化中TGF-受体1（TGFBR1）的信号传导。
方法：超声心动图，苏木精-伊红（HE）和Masson三色染色用于评估EF对MI感染小鼠体内心脏结构和功能的影响。细胞增殖试验(MTS),5-乙炔基-2'-脱氧尿苷（EdU），采用蛋白质印迹技术检测EF对天然心脏成纤维细胞（CFs）增殖和胶原沉积的影响。分子模拟和表面等离子体共振成像（SPRi）用于探索TGFBR1和EF相互作用。利用心脏特异性Tgfbr1敲除小鼠(Tgfbr1ΔMCK)来证明EF的影响。
结果：体内实验表明EF减轻了心肌纤维化，改善MI后的心功能不全，并以剂量依赖性方式下调TGFBR1信号传导。此外，体外实验表明，EF显著抑制CFs的增殖，胶原沉积和TGFBR1信号传导，随后是TGF-β1刺激。更具体地说,分子模拟,分子动力学,和SPRi共同显示EF直接靶向TGFBR1。最后,敲低Tgfbr1可部分逆转EF对MI小鼠心肌纤维化的抑制活性。
结论：EF通过直接抑制TGFBR1及其下游信号通路减轻MI后心肌纤维化。
目的：本研究的目的是探讨EF如何影响MI后心肌纤维化中TGF-受体1（TGFBR1）的信号传导。
方法：超声心动图，苏木精-伊红（HE）和Masson三色染色用于评估EF对MI感染小鼠体内心脏结构和功能的影响。细胞增殖试验(MTS),5-乙炔基-2'-脱氧尿苷（EdU），采用蛋白质印迹技术检测EF对天然心脏成纤维细胞（CFs）增殖和胶原沉积的影响。分子模拟和表面等离子体共振成像（SPRi）用于探索TGFBR1和EF相互作用。利用心脏特异性Tgfbr1敲除小鼠(Tgfbr1ΔMCK)来证明EF的影响。
结果：体内实验表明EF减轻了心肌纤维化，改善MI后的心功能不全，并以剂量依赖性方式下调TGFBR1信号传导。此外，体外实验表明，EF显著抑制CFs的增殖，胶原沉积和TGFBR1信号传导，随后是TGF-β1刺激。更具体地说,分子模拟,分子动力学,和SPRi共同显示EF直接靶向TGFBR1。最后,敲低Tgfbr1可部分逆转EF对MI小鼠心肌纤维化的抑制活性。
结论：EF通过直接抑制TGFBR1及其下游信号通路减轻MI后心肌纤维化。
