论文标题：Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway in vivo and in vitro

期刊： Frontiers of Medicine

作者：Fen Zhang, Lanlan Xiao, Ya Yang, Menghao Zhou, Yalei Zhao, Zhongyang Xie, Xiaoxi Ouyang, Feiyang Ji, Shima Tang, Lanjuan Li

发表时间：15 Jun 2023

DOI：10.1007/s11684-022-0953-y

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浙江大学医学院附属第一医院李兰娟团队在Frontiers of Medicine发表研究论文《宫血干细胞通过JNK/MAPK信号通路缓解自身免疫性肝炎》（Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway in vivo and in vitro）。本文通过构建刀豆蛋白A（Con A）诱导的自身免疫性肝炎（AIH）小鼠模型，发现宫血干细胞（MenSCs）可降低小鼠死亡率、改善肝功能，其作用机制主要与抑制c-Jun N端激酶/丝裂原活化蛋白激酶（JNK/MAPK）信号通路介导的肝细胞凋亡有关。

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.

自身免疫性肝炎（AIH）是一种在全球范围内分布的严重肝脏疾病，可发生于任何年龄段。宫血干细胞（MenSCs）已在急性肺损伤和肝衰竭的治疗中显示出疗效。然而，其在AIH治疗效果中的作用仍不明确。本研究通过静脉注射刀豆蛋白A（Con A）构建了经典的AIH小鼠模型。在治疗组中，于注射Con A的同时静脉注射MenSCs。结果显示，MenSCs治疗显著降低了因注射Con A导致的死亡率，并且肝功能检查和组织学分析结果也有所改善。磷酸化蛋白质组学分析和RNA测序结果显示，MenSCs主要通过凋亡和c-Jun N端激酶/丝裂原活化蛋白激酶（JNK/MAPK）信号通路来改善AIH。细胞凋亡分析表明，注射Con A使裂解的半胱天冬酶3的蛋白表达增加，而MenSCs移植可降低其表达，这与TUNEL染色结果一致。采用AML12共培养系统和JNK抑制剂（SP600125）验证了JNK/MAPK和细胞凋亡的信号通路。研究结果表明，MenSCs可能是治疗AIH的一种有前景的策略。

期刊介绍

Frontiers of Medicine专注于发表临床医学和基础医学领域的最新研究成果，旨在通过全球医疗专业人员之间的交流促进健康和医疗保健的发展。该刊采用严格的同行评审和编辑流程，确保发表的文章的科学准确性、新颖性和重要性。

原文信息

标题

Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway in vivo and in vitro

作者

Fen Zhang¹, Lanlan Xiao¹, Ya Yang¹, Menghao Zhou¹, Yalei Zhao^1,2, Zhongyang Xie¹, Xiaoxi Ouyang¹, Feiyang Ji³, Shima Tang¹, Lanjuan Li¹

机构

1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

2. Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xian Jiaotong University, Xian 710049, China

3. Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Zhejiang, Hangzhou 310016, China

通讯作者

Lanjuan Li

引用这篇文章

Fen Zhang, Lanlan Xiao, Ya Yang, Menghao Zhou, Yalei Zhao, Zhongyang Xie, Xiaoxi Ouyang, Feiyang Ji, Shima Tang, Lanjuan Li. Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway in vivo and in vitro. Front. Med., 2023, 17(3): 534–548

https://doi.org/10.1007/s11684-022-0953-y

https://journal.hep.com.cn/fmd/EN/10.1007/s11684-022-0953-y

https://link.springer.com/article/10.1007/s11684-022-0953-y

感谢作者对Frontiers of Medicine的信任和支持。

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