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.
Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710049, China.
Front Med. 2023 Jun;17(3):534-548. doi: 10.1007/s11684-022-0953-y. Epub 2023 Apr 3.
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）是一种严重的全球分布的肝脏疾病，可发生于任何年龄。人月经血来源的干细胞（MenSCs）在急性肺损伤和肝衰竭中显示出治疗效果。然而，它们在 AIH 疗效中的作用尚不清楚。在这里，通过静脉注射伴刀豆球蛋白 A（Con A）构建了经典的 AIH 小鼠模型。在治疗组中，同时给予 Con A 注射和 MenSCs 静脉注射。结果表明，MenSCs 治疗可显著降低 Con A 注射引起的死亡率，改善肝功能试验和组织学分析。磷酸化蛋白质组学分析和 RNA-seq 的结果表明，MenSCs 通过细胞凋亡和 c-Jun N 末端激酶/丝裂原活化蛋白信号通路改善 AIH。凋亡分析表明，Con A 注射增加了 cleaved caspase 3 的蛋白表达，MenSCs 移植减少了其表达，与 TUNEL 染色结果一致。使用 AML12 共培养系统和 JNK 抑制剂（SP600125）验证了 JNK/MAPK 和细胞凋亡信号通路。这些发现表明，MenSCs 可能是 AIH 的一种有前途的治疗策略。
