HSD17B13 液-液相分离促进白细胞粘附在慢性肝炎的肝炎
Jing Ye1, Xiyu Huang1, Manman Yuan1
1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
Journal of molecular cell biology
|May 1, 2024
概括
在脂质液滴周围,HSD17B13蛋白形成液-液相分离 (LLPS),通过增加血小板激活因子 (PAF) 来驱动代谢功能障碍相关的脂肪肝炎 (MASH) 中的肝炎. 准这个过程可以治疗肝脏疾病.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 这种HSD17B13 rs72613567:TA多态性与降低肥胖症向代谢功能障碍相关的肥胖肝炎 (MASH) 的进展有关.
- 对于HSD17B13在引发肝炎中的确切病原性作用尚未完全阐明.
研究的目的:
- 确定HSD17B13在引发肝炎中的致病作用.
- 研究HSD17B13对肝病进展的分子机制.
主要方法:
- 在MASH患者肝脏中的脂质滴周围观察HSD17B13液态液态相分离 (LLPS).
- 评估HSD17B13二分化及其对酶功能的影响.
- 评估血小板激活因子 (PAF) 生物合成及其对纤维素原合成和白细胞粘附的下游影响.
- 针对PAF受体和STAT3通路的抑制研究.
- 在体内实验中使用小鼠的腺相关病毒介导的HSD17B13的外表.
主要成果:
- 在MASH患者的肝脏中,HSD17B13围绕脂质滴形成LLPS,由二分化促进.
- HSD17B13 LLPS增强了PAF生物合成,导致纤维素合成和白细胞粘附的增加.
- 阻断PAF受体或STAT3通路可以减轻纤维素合成和白细胞粘附.
- 在小鼠中,HSD17B13的异位表达加剧了饮食/CCl4诱导的肝炎.
结论:
- HSD17B13 LLPS是通过PAF介导的白细胞粘附导致肝炎的关键驱动因素.
- 准HSD17B13阶段过渡是慢性肝病中肝炎的潜在治疗策略.
更多相关视频
11:38A Flow Adhesion Assay to Study Leucocyte Recruitment to Human Hepatic Sinusoidal Endothelium Under Conditions of Shear Stress
Published on: March 21, 2014
15.4K
11:44Long Term Intravital Multiphoton Microscopy Imaging of Immune Cells in Healthy and Diseased Liver Using CXCR6.Gfp Reporter Mice
Published on: March 24, 2015
12.0K
相关概念视频
Hepatitis
99
Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver.
99
Cirrhosis II: Pathophysiology
53
Cirrhosis is a progressive chronic liver injury caused by prolonged inflammation, excessive fibrotic remodeling, and impaired regeneration. Over time, repeated hepatic insults disrupt the liver’s architecture and function, leading to reduced blood flow, impaired bile drainage, and diminished metabolic capacity.Pathophysiology of cirrhosisCirrhosis arises from three main responses to chronic liver damage: inflammation, immune activation, and hepatocyte death. These processes lead to...
53
