瑞索尔D2-G蛋白结合受体18增强骨髓功能,并限制肥胖症和肝脏原积累在衰老
Hannah Fitzgerald1, Jesse L Bonin2, Sayeed Khan1
1The Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York.
The American journal of pathology
|September 17, 2023
概括
衰老会通过炎症导致肝损伤. 针对GPR18的Resolvin D2 (RvD2) 疗法通过促进老年小鼠的巨细胞修复机制来降低肝硬化和纤维化.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 衰老研究研究 衰老研究
背景情况:
- 衰老的特点是慢性炎症和组织功能受损.
- 溶素D2 (RvD2) 是解决炎症的关键调解剂,通过GPR18受体起作用.
- 随着年龄的增长,GPR18表达的增加与肝脏脂肪和纤维化有关.
研究的目的:
- 研究RvD2-GPR18信号传递在与年龄相关的肝功能障碍中的作用.
- 为了确定RvD2是否可以改善老年小鼠的肥胖和纤维化.
- 阐明RvD2影响肝脏修复的机制.
主要方法:
- RNA测序以评估老年小鼠和人类肝脏样本中的Gpr18表达.
- 在中年老鼠的髓状细胞中对GPR18进行基因操纵.
- 在老化小鼠模型中使用RvD2治疗.
- 流细胞计和移植检测分析免疫细胞群和骨髓功能.
主要成果:
- 在老化的大细胞和老年人肝脏中,Gpr18表达被上调,与肥胖症和纤维化相关.
- 骨髓细胞中GPR18的丧失加剧了肝脏脂肪和纤维化.
- 通过RvD2治疗,减少了肥胖症和纤维化,增加了Mac2+巨细胞,单细胞衍生巨细胞和单细胞.
- RvD2刺激了骨髓原始体,增强了单细胞-巨细胞分化.
结论:
- RvD2-GPR18信号传递是与年龄相关的肝硬化症和纤维化症的关键调节者.
- 通过调节免疫细胞群和骨髓功能,RvD2疗法促进肝脏的修复.
- 针对RvD2-GPR18信号提供了与年龄相关的肝病的潜在治疗策略.
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