富含histidine的糖蛋白在与代谢功能障碍相关的脂肪肝炎相关的疾病进展和肝癌发生过程中
Beatrice Foglia1, Salvatore Sutti2, Stefania Cannito1
1Department Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Torino, Italy.
Frontiers in immunology
|March 12, 2024
概括
富含希斯蒂丁的葡萄糖蛋白 (HRG) 通过支持炎症性巨细胞,促进了与代谢功能障碍相关的脂肪性肝病 (MASLD) 到肝癌的进展. 较低的HRG水平可能表明与MASLD相关的肝细胞癌 (HCC) 患者的结果更好.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD),以前称为NAFLD,是一个全球性的健康问题.
- MASLD可以发展为MASH (以前称为NASH),导致纤维化,肝硬化,肝衰竭和HCC.
- 胺丰富的葡萄糖蛋白 (HRG) 在MASLD/MASH进展和HCC发展中的作用需要研究.
研究的目的:
- 研究胺丰富的糖蛋白 (HRG) 在MASLD/MASH向肝细胞癌 (HCC) 的进展中的作用.
- 评估HRG作为MASLD/MASH相关的HCC的潜在预后标志物.
主要方法:
- 在MASH和肝癌发生的特定饮食和化学诱导协议下利用了HRG淘汰赛 (HRG-/-) 小鼠.
- 检查了用净化HRG处理的THP1单细胞.
- 分析了患有HCC和没有HCC的MASLD患者的良好特征队列,包括对血HRG水平和周围瘤组织HRG阳性的评估.
主要成果:
- 随着MASLD/MASH的进展,HRG水平显著增加,与纤维化/肝硬化严重程度相关.
- HRG淘汰赛小鼠表现出降低的HCC发育,其特征是炎症性巨细胞透率降低和血管生成受损.
- 与MASH相关的HCC在周围瘤组织中的更高HRG阳性与患者存活率降低和复发率增加相关.
- 与早期纤维化阶段 (F0/F1) 相比,在肝硬化 (F4) 患者和HCC患者中观察到血HRG水平升高.
结论:
- HRG通过促进具有促炎和促血管功能的瘤相关巨细胞,显著促进MASLD/MASH向HCC的进展.
- 在MASLD/MASH相关的HCC中,HRG支持癌细胞存活.
- HRG显示出作为MASLD/MASH. HCC患者的预后预测指标的前景.
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