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在代谢功能障碍相关的脂肪肝炎中,衰老性肝星细胞的表型和本体发生

Chittampalli N Yashaswini¹, Tianyue Qin², Dipankar Bhattacharya³

¹Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Medical Scientist Training Program, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Journal of hepatology

|March 20, 2024

概括

衰老的肝星细胞 (HSC) 在代谢功能障碍相关的脂肪肝炎 (MASH) 中驱动肝纤维化. 这些细胞来源于激活的HSCs,并表达像UPAR这样的特定标记物,为肝脏疾病提供新的治疗点.

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
免疫学免疫学免疫学

背景情况:

代谢功能障碍相关的脂肪肝炎 (MASH) 是肝癌的日益严重的原因,由肝星细胞 (HSC) 驱动.
一个HSC的子集变得衰老,导致肝纤维化和肝细胞癌 (HCC).
针对衰老的HSC对MASH治疗有希望,但它们的特征和起源需要详细研究.

研究的目的:

在人类和小鼠MASH中全面描述衰老的HSCs的表型和细胞起源.
在衰老的HSC上确定新的治疗点.

主要方法:

综合老化标志物,免疫染,流细胞计和单核RNA测序 (snRNAseq).
应用了伪时间轨迹分析来确定HSC本体发生.
在MASH中绘制了尿素激酶类型等离子体激活受体 (uPAR) 的表达模式.

主要成果:

经证实,在MASH模型中,衰老的HSC是由激活的HSC产生的.
uPAR的表达随着疾病的发展而演变,最初特定于HSC,后来在髓状细胞上发现.
在衰老的HSC上鉴定出新的表面蛋白,包括曼诺酶受体CD206,作为潜在的治疗点.

结论:

定义了MASH中HSC衰老的关键特征,为抗纤维菌疗法提供了基础.
突出了UPAR和其他新型表面蛋白质作为衰老的HSC枯竭的目标.

关键词:

CD206 是一个CD206 CD206 是一个CD206 CD206 肝脏的恒星细胞.与代谢功能障碍相关的脂肪肝炎.衰老是一种老化.一个老年化的老年主义者.在 uPAR 中,PAR 是PAR.

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