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在肝星细胞中CEACAM1的条件删除会导致它们的激活

Harrison T Muturi¹, Hilda E Ghadieh², Suman Asalla¹

¹Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.

Molecular metabolism

|August 21, 2024

概括

肝星细胞 (HSC) 中CEACAM1的损失会激活它们,促进肝纤维化. 这通过表皮生长因子受体 (EGFR) 途径发生,独立于胰岛素耐药性或稳定性.

科学领域:

肝病学肝病学是一种肝病学.
细胞生物学细胞生物学
纤维化研究纤维化研究

背景情况:

肝脏CEACAM1 (癌胚性抗原细胞粘附分子1) 表达与晚期代谢功能障碍相关的脂肪肝炎 (MASH) 纤维化下降.
肝细胞中CEACAM1的缺乏会导致胰岛素耐药性,肥胖症,炎症和纤维化.
PPARγ (Peroxisome增殖器激活受体马) 影响CEACAM1转录和HSC静止.

研究的目的:

调查肝星细胞 (HSC) 中的CEACAM1损失是否导致它们的激活.
确定CEACAM1在MASH进展期间在HSC中的作用.

主要方法:

在培养的人类LX2星状细胞 (KD-LX2) 中检查了CEACAM1下调.
产生的LratCre+Cc1fl/fl突变小鼠具有条件的HSC特异性的Ceacam1删除.
利用媒体传输实验来评估HSC激活潜力.

主要成果:

突变小鼠表现出肝炎和纤维化,但没有胰岛素耐药性或肉脂症.
来自突变细胞和KD-LX2细胞的HSC显示了肌纤维细胞转化.
来自激活HSC的介质诱导了野生类型的HSC激活.
尼古丁酸和gefitinib (EGFR抑制剂) 治疗通过调节IL-6,脂肪酸和EGFR/NF-κB/STAT3通路来抑制HSC激活.

结论:

在HSC中CEACAM1损失会诱导肌纤维细胞的转化,导致肝纤维化.
这种激活由自身隐性EGFR通路介导,放大炎症和扩散.
该机制独立于胰岛素耐药性和肝硬化症运作.

关键词:

肝脏纤维化肝脏纤维化肝脏肥胖症肝脏肥胖症炎症炎症是一种炎症.网红酸是什么意思网红酸是什么意思星状细胞的增殖星状细胞的增殖

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