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由脱氧醇酸激活的肠干细胞中的ABL1 - YAP1轴有助于肝硬化

Tiancheng Mao^1,2, Xianjun Xu³, Leheng Liu^1,2

¹Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

Journal of translational medicine

|December 20, 2024

概括

通过脱氧醇酸激活肠干细胞中的ABL1-YAP1轴,有助于脂肪肝疾病. 针对这一轴可能为与代谢功能障碍相关的脂肪肝疾病提供新的治疗策略.

科学领域:

胃肠病学胃肠病学
肝病学肝病学是一种肝病学.
分子生物学分子生物学

背景情况:

是的相关蛋白1 (YAP1) 对于细胞存活和增殖至关重要,并与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 有关.
在这项研究之前,肠道YAP1在MAFLD病变发生中的特定作用在很大程度上是未知的.

研究的目的:

调查肠道YAP1在MAFLD发展中的作用.
阐明肠道YAP1影响MAFLD肠肝轴的分子机制.

主要方法:

在MAFLD患者和健康个体中比较肠道YAP1激活.
利用YAP1淘汰赛小鼠食高脂肪饮食 (HFD) 和脱氧醇酸 (DCA) 来研究肠肝轴变化.
采用了免疫光,西部斑点,RT-qPCR,ELISA,16SrDNA测序和细胞培养技术.

主要成果:

在MAFLD患者和HFD养小鼠中观察到肠道YAP1激活.
在小鼠中YAP1淘汰赛缓解了HFD诱导的肝肥胖症和肠肝轴功能障碍 (减少LPS,炎症,改变肠道微生物群,损害ISC分化).
脱氧胆酸 (DCA) 模仿了HFD效应,激活了骨中的阿贝尔森氨酸蛋白激酶1 (ABL1) -YAP1轴,抑制了肠道干细胞的分化.

结论:

由DCA激活的肠干细胞中的ABL1-YAP1轴通过肠-肝轴促进肝肥胖症.
这个轴为管理MAFLD提供了一个潜在的新型肠道治疗点.

关键词:

脱氧胆酸是一种脱氧胆酸.肝脏肥胖症肝脏肥胖症有高脂肪的饮食.肠道干细胞是肠道干细胞.是的相关蛋白1 是的相关蛋白1

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