Abstract：
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.
摘要：
自身免疫性肝炎（AIH）是一种严重的全球分布的肝病，可发生在任何年龄。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作用。然而,它们在AIH疗效中的作用尚不清楚.这里,通过静脉注射伴刀豆球蛋白A（ConA）构建了经典的AIH小鼠模型。在治疗组中,静脉内注射MenSC,同时注射ConA。结果表明，通过MenSCs治疗，ConA注射的死亡率显着降低，肝功能测试和组织学分析也得到改善。磷酸化蛋白质组分析和RNA-seq结果表明，MenSCs改善了AIH，主要通过细胞凋亡和c-Jun氨基末端激酶/丝裂原活化蛋白信号通路。细胞凋亡分析表明，ConA注射可增加caspase3的蛋白表达，而MenSCs移植可减少caspase3的表达。与TUNEL染色结果一致。使用AML12共培养系统和JNK抑制剂(SP600125)来验证JNK/MAPK和凋亡信号通路。这些发现表明，MenSCs可能是AIH的一个有希望的策略。
