在绝经后心肌病中,Prmt7调节了JAK/STAT/Socs3信号通路
Byeong-Yun Ahn1, Yan Zhang1, Shibo Wei1
1Department of Molecular Cell Biology, Sungkyunkwan University, School of Medicine, Suwon, Republic of Korea.
Experimental & molecular medicine
|March 15, 2024
概括
蛋白质氨酸甲基转移酶7 (Prmt7) 以性别特定的方式保护心脏病. 由于影响JAK/STAT通路,Prmt7缺乏导致心肌病,特别是在男性和绝经后女性中.
科学领域:
- 心血管生物学 心血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子医学是分子医学.
背景情况:
- 蛋白质氨酸甲基转移酶 (PRMT) 是细胞过程的关键调节者,包括应激反应.
- 绝经相关心肌病是一种严重的健康问题,特别是在老年人群中.
- 对于PRMT7在心脏健康中的特殊作用及其性别特异性调节仍然在很大程度上未被探索.
研究的目的:
- 研究蛋白质氨酸甲基转移酶7 (Prmt7) 在预防更年期相关心肌病的作用.
- 阐明Prmt7缺乏对心脏功能和结构的性别特异性影响.
- 为了确定 Prmt7 的心脏保护作用背后的分子机制.
主要方法:
- 生产心脏特异性Prmt7淘汰赛 (cKO) 鼠标,以评估心脏功能和病理.
- 使用心肌细胞进行体外研究,以评估Prmt7抑制对氧化应激和DNA损伤的影响.
- 在卵巢切除小鼠和Prmt7缺乏心肌细胞中进行转录组分析和JAK/STAT信号通路评估.
- 评估17β-雌二醇 (E2) 对Prmt7表达和心脏毒性的影响.
主要成果:
- 心脏特异性Prmt7切除 (cKO) 导致性别特异性心肌病,雄性cKO小鼠表现出心脏功能受损,过度缩小和纤维化.
- 雌性cKO小鼠表现出类似的表型,主要是在绝经或卵巢切除 (OVX) 后.
- 抑制Prmt7加剧了多克索鲁比 (DOX) 诱导的心脏毒性,氧化应激和心肌细胞中的DNA损伤.
- Prmt7通过控制细胞因子信号3 (Socs3) 抑制剂表达来调节JAK/STAT信号通路.
- Prmt7的消耗取消了17β-雌激醇 (E2) 对DOX诱导的心脏毒性的保护作用.
结论:
- Prmt7在心脏保护中发挥着关键的性别特异性作用,防止与更年期相关的损伤.
- Prmt7的机制涉及通过Socs3.3调节JAK/STAT信号通路.
- Prmt7成为心力衰竭的潜在治疗点,考虑性别特定的方法.
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