伸展诱导的肝脏内皮内分泌机制促进肝细胞的增殖
Yi Wu1,2, Linda Li1, Wang Li1,2
1Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
Hepatology (Baltimore, Md.)
|September 9, 2024
概括
在再生过程中对肝细胞的机械拉伸通过YAP核转移调节肝素结合型EGF类生长因子 (HB-EGF),促进肝脏的再生. 这揭示了肝脏再生的关键机制.
科学领域:
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
- 机械生物学 机械生物学
背景情况:
- 部分肝切除术触发肝脏再生,增加血液流动,并机械拉伸肝脏侧侧内皮细胞 (LSECs).
- 肝素结合EGF类似生长因子 (HB-EGF) 对于肝脏再生至关重要.
研究的目的:
- 调查LSECs上的机械拉伸是否促进HB-EGF分泌.
- 阐明这种反应背后的分子机制.
主要方法:
- 在体内和体外肝脏再生模型,在体内LSEC机械拉伸.
- 检测HB-EGF表达和肝细胞增殖.
- 机械敏感蛋白的阻断/抑制,包括YAP和β1-整体蛋白.
主要成果:
- 在LSEC中,机械拉伸剂量依赖增加了HB-EGF.
- 这种上调调节是由YES关联蛋白 (YAP) 核转位介导的.
- YAP转位涉及F-actin聚合,核孔扩张和BAG3上调,其中β1-整体素是关键的机制传感器.
- 内皮细胞特异性Yap1缺陷减弱HB-EGF促进的肝脏再生.
结论:
- 机械拉伸通过YAP转位诱导LSEC中的HB-EGF分泌.
- 这一过程以机械克林的方式促进了肝细胞的增殖.
- 这些发现加深了对肝脏再生中的机械生物合的理解.
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