在巨细胞中GPER1的激活改善了UUO诱导的纤维化
Lin Xie1,2, Ye Cheng1,3, Wen Du2
1Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
Cell death & disease
|December 12, 2023
概括
向巨细胞中的G蛋白结合雌激素受体1 (GPER1) 减少纤维化. 激活GPER1抑制M1和M2巨细胞的激活,为纤维化提供了潜在的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 巨细胞在纤维化中起着关键作用.
- 与G蛋白结合的雌激素受体1 (GPER1) 调节巨细胞活动和炎症.
- 在巨细胞驱动纤维化中GPER1的具体作用尚不清楚.
研究的目的:
- 在单边尿路阻塞 (UUO) 诱导的纤维化模型中研究巨GPER1的功能.
- 为了确定GPER1激活是否可以减轻巨细胞介导纤维化.
主要方法:
- 使用卵巢切除 (OVX) 的雌性和雄性小鼠接受了UUO.
- 使用GPER1激动剂 (G-1) 或使用Gper1缺失的小鼠.
- 在实验室中进行了涉及巨分离,RNA测序,免疫阻塞和与管状上皮细胞和纤维细胞共同培养的试验.
主要成果:
- 在UUO小鼠中,GPER1激活 (G-1治疗) 减少了纤维化病变和M1/M2巨细胞透.
- 在雄性UUO小鼠中,Gper1缺失加剧了纤维化和炎症.
- 在体外,GPER1激活抑制了M0巨细胞的两极分化,并降低了免疫和MAPK通路的调节,保护了管状细胞并减少了纤维细胞细胞外细胞矩阵表达.
结论:
- 这项研究是第一个证明GPER1对巨细胞介导纤维化有抑制作用的研究.
- GPER1激活抑制了M1和M2巨细胞的激活,减轻了损伤和纤维化.
- GPER1代表了治疗纤维化的潜在治疗标.
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