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

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.

Keywords

autoimmune hepatitis (AIH) / concanavalin A (Con A) / human menstrual blood-derived stem cells (MenSCs) / apoptosis / mitogen-activated protein kinase (MAPK)

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Acknowledgements

This project was supported by Science Fund for Creative Research Groups of the National Natural Science Foundation of China (No. 81721091) and The Independent Task of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine. The authors wish to thank Charlie Xiang’s laboratory for kindly providing human MenSCs and Tsingke Biological Technology for the RNA-seq and data processing.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-022-0953-y and is accessible for authorized users.

Compliance with ethics guidelines

Fen Zhang, Lanlan Xiao, Ya Yang, Menghao Zhou, Yalei Zhao, Zhongyang Xie, Xiaoxi Ouyang, Feiyang Ji, Shima Tang and Lanjuan Li declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

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