内皮细胞Birc3通过调节Drp1-介导的线粒体裂变通过MAPK/PI3K/Akt路径促进纤维化
Shuai Chen1, Qingqing He2, Huaiyu Yang3
1Department of Urology, Zhongshan People's Hospital, Zhongshan 528400, China.
Biochemical pharmacology
|August 11, 2024
概括
含有3 (Birc3) 的百科病毒IAP重复促进纤维化,通过驱动内皮-介质酶过渡和线粒体功能障碍来促进纤维化. 抑制Birc3可能为慢性病提供一种新的治疗方法.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 纤维化是慢性病 (CKD) 进展的常见途径.
- 内皮 - 介质细胞过渡 (EndMT) 生成肌纤维细胞,促进纤维生成.
- 百科病毒IAP重复含有3 (Birc3) 已知可以调节细胞死亡和炎症,但其通过EndMT在纤维化中的作用尚不清楚.
研究的目的:
- 通过EndMT调查Birc3在间胞纤维化中的作用.
- 阐明EndMT和线粒体动态中的Birc3的潜在分子机制.
主要方法:
- 利用单边尿道阻塞 (UUO) 鼠标模型和转化生长因子-β (TGF-β) 诱导的EndMT在人类静脉内皮细胞 (HUVECs) 中.
- 评估了Birc3表达,EndMT标志物 (α-SMA,CD31) 和线粒体分裂 (Drp1).
- 研究了MAPK/PI3K/Akt信号通路的参与.
主要成果:
- 在纤维化脏和TGF-β治疗的HUVEC中观察到Birc3表达和EndMT标记的升高.
- 在体内和体外,Birc3敲击抑制了EndMT和胺相关蛋白1 (Drp1) 介导的线粒体裂变.
- 内皮细胞Birc3通过TGF-β刺激细胞中的MAPK/PI3K/Akt通路促进了Drp1诱导的线粒体裂变.
结论:
- 伯克3通过加剧EndMT和线粒体分裂,在促进纤维化方面发挥着关键作用.
- 向Birc3为改善内皮细胞存活率和减轻CKD进展提供了潜在的治疗策略.
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