探索细胞可塑性在与代谢功能障碍相关的肥胖症和相关分子机制中的作用
Merve Ercin1, Selda Gezginci-Oktayoglu2
1Molecular Biology Section, Biology Department, Faculty of Science, Istanbul University, Istanbul, Turkey.
Journal of translational medicine
|November 13, 2025
概括
长期高胰岛素会导致肝脏前代细胞样肝细胞脱. 随后的脂肪酸暴露通过特定的分子途径促进脂肪生成和纤维生成.
科学领域:
- 肝病学和细胞生物学.
- 慢性肝病的分子机制慢性肝病的分子机制
背景情况:
- 慢性疾病中的肝细胞可以分化为类似肝细胞的肝细胞 (LPC).
- 这项研究调查了肝细胞是否在长期高胰岛素下分离,并在脂肪酸暴露时形成脂肪细胞或纤维细胞.
研究的目的:
- 为了确定慢性高胰岛素刺激是否诱导肝细胞脱差.
- 为了研究由脂肪酸暴露引起的脂肪细胞和/或纤维细胞样细胞的随后形成.
- 为了阐明这些细胞转换所涉及的分子途径.
主要方法:
- 治疗 HepG2 细胞时,给予长时间的高胰岛素,然后给予油酸 (OA).
- 测量了LPC,脂肪细胞和纤维细胞标记物的基因表达.
- 使用抑制剂分析了细胞群 (CD34+,PDGFR1α+,FAPα+),脂质积累和蛋白质水平.
主要成果:
- 高胰岛素增加LPC标记物和减少肝细胞标记物.
- 在高胰岛素后的OA导致脂质积累,脂肪生成和脂肪细胞标记物 (Perilipin-A) 的增加.
- 甲状腺暴露增加了纤维细胞标记物和FAPα+细胞;TLR4,GSK3β和β-catenin通路参与其中.
结论:
- 长期高胰岛素驱动肝细胞去分化成纤维基原始细胞.
- 脂肪酸暴露通过TLR4/GSK3β促进脂肪生成,通过TLR4/β-catenin通路促进纤维生成.
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