再思考肉毒碱棕榈酰基转移酶II和肝干细胞在代谢功能障碍相关的脂肪肝相关肝细胞癌中的作用

IF 5.4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hong Cai, Chun-Hui Yang, Peng Gao
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引用次数: 0

摘要

本文讨论了Wang等人最近的一项研究,该研究揭示了代谢功能障碍相关的脂肪性肝病(MAFLD)向肝细胞癌(HCC)发展的代谢和免疫机制。该研究强调了线粒体肉碱棕榈酰基转移酶II (CPT II)失活的作用,CPT II激活以CD44和CD24表达为标志的肝癌干细胞,促进HCC的发展。Wang等人利用动态小鼠模型和临床样本,发现CPT II下调、线粒体膜电位改变和肝内CD4+ T细胞减少是疾病进展的关键驱动因素。研究结果将这些变化与类固醇生物合成和p53信号传导联系起来,从而导致t细胞功能障碍和免疫抑制。本文强调了这些结果与了解MAFLD发病机制的相关性,并讨论了针对CPT II活性、线粒体功能和免疫监测的潜在治疗策略,以预防或减轻晚期MAFLD中HCC的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Rethinking carnitine palmitoyltransferase II and liver stem cells in metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma.

This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease (MAFLD) to hepatocellular carcinoma (HCC). The study highlights the role of mitochondrial carnitine palmitoyltransferase II (CPT II) inactivity, which activates liver cancer stem cells marked by cluster of differentiation 44 (CD44) and CD24 expression, promoting HCC development. Using dynamic mouse models and clinical samples, Wang et al identified CPT II downregulation, mitochondrial membrane potential alterations, and reduced intrahepatic CD4+ T cell as key drivers of disease progression. The findings link these changes to steroid biosynthesis and p53 signaling, contributing to T-cell dysfunction and immunosuppression. This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT II activity, mitochondrial function, and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.

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来源期刊
World Journal of Gastroenterology
World Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
7.80
自引率
4.70%
发文量
464
审稿时长
2.4 months
期刊介绍: The primary aims of the WJG are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in gastroenterology and hepatology.
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