在肝脏纤维化中起着至关重要的作用
Meng Xu1, Hong-Hai Xu2, Yuan Lin3
1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong 510515, China.
通过与Tie1受体相互作用而加剧肝纤维化. 针对这种LECT2/Tie1途径为肝纤维化提供了潜在的治疗策略.
科学领域:
- 肝病学
- 分子生物学
- 内皮细胞生物学
背景情况:
- 全球有数百万人患有肝纤维化, 由于分子机制不明, 缺乏有效的治疗方法.
- 内皮细胞 (EC) 特定的孤儿受体,如Tie1,在肝脏病理学中发挥关键作用.
- 鉴定新的分子参与者对于开发肝纤维化治疗措施至关重要.
研究的目的:
- 研究白细胞衍生化学素2 (LECT2) 在肝纤维化中的作用.
- 阐明LECT2与Tie1受体之间的相互作用.
- 评估LECT2/Tie1信号作为肝纤维化的潜在治疗标.
主要方法:
- 研究LECT2作为内皮细胞中Tie1受体的配体.
- 在体内使用小鼠模型 (LECT2过度表达和绝杀) 来研究纤维化进展.
- 使用腺相关病毒载体血清型9 (AAV9) - LECT2小毛RNA (shRNA) 进行治疗.
- 与人类肝纤维化分期相关的LECT2表达.
主要成果:
- LECT2与Tie1结合,破坏Tie1/Tie2异体化并促进Tie2同体化.
- PPAR信号的LECT2激活抑制了EC迁移和管的形成.
- 通过影响血管生成和毛细化,LECT2的过度表达会使肝纤维化恶化; Lect2- KO小鼠显示逆转变化.
- 在体内,AAV9- LECT2小RNA治疗显著降低了纤维化.
- 血清LECT2水平升高与晚期肝纤维化相关.
结论:
- LECT2是Tie1的功能性连接体,在肝脏中介助纤维化作用.
- 准LECT2/Tie1信号通路为肝纤维化提供了一个有前途的治疗途径.
- 血清LECT2水平可以作为肝纤维化查和诊断的有价值的生物标志物.
相关概念视频
13:09Rat Liver Perfusion and Primary Hepatocytes Isolation: An Old Procedure Crucial for Cutting-Edge 3D Organoids Culture
12:35In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion
12:36Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Ligand Binding and Linkage


