Copyright
©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Yiguanjian decoction enhances fetal liver stem/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state
Ying Xu, Wei-Wei Fan, Wen Xu, Shi-Li Jiang, Gao-Feng Chen, Cheng Liu, Jia-Mei Chen, Hua Zhang, Ping Liu, Yong-Ping Mu
Ying Xu, Wei-Wei Fan, Wen Xu, Shi-Li Jiang, Gao-Feng Chen, Cheng Liu, Jia-Mei Chen, Hua Zhang, Ping Liu, Yong-Ping Mu, Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Ying Xu, Wei-Wei Fan, Wen Xu, Shi-Li Jiang, Gao-Feng Chen, Cheng Liu, Jia-Mei Chen, Hua Zhang, Ping Liu, Yong-Ping Mu, Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Ying Xu, Wei-Wei Fan, Wen Xu, Shi-Li Jiang, Gao-Feng Chen, Cheng Liu, Jia-Mei Chen, Hua Zhang, Ping Liu, Yong-Ping Mu, Key Laboratory of Liver and Kidney Disease of the Ministry of Education, Shanghai 201203, China
Ying Xu, Wei-Wei Fan, Wen Xu, Shi-Li Jiang, Gao-Feng Chen, Cheng Liu, Jia-Mei Chen, Hua Zhang, Ping Liu, Yong-Ping Mu, Clinical Key Laboratory of TCM of Shanghai, Shanghai 201203, China
Author contributions: Mu YP and Liu P designed the research; Xu Y, Fan WW, Xu W, and Chen JM performed the research; Zhang H contributed analytic tools; Chen GF performed pathological analysis; Mu YP, Xu Y, Jiang SL, and Liu C analyzed the data; Mu YP and Xu Y composed the paper.
Supported by the National Natural Science Foundation of China, No. 81173223, No. 81573948, and No. 81874390.
Institutional animal care and use committee statement: The experimental protocol was approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (No. 20130132).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines and prepared the manuscript accordingly.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yong-Ping Mu, PhD, Associate Chief Physician, Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong district, Shanghai 201203, China.
ypmu8888@126.com
Telephone: +86-21-20256526 Fax: +86-21-20256521
Received: August 8, 2018
Peer-review started: August 8, 2018
First decision: October 5, 2018
Revised: October 19, 2018
Accepted: October 26, 2018
Article in press: October 26, 2018
Published online: November 14, 2018
Processing time: 97 Days and 5.5 Hours
AIM
To investigate whether Yiguanjian decoction (YGJ) has an anti-liver cirrhotic effect and whether it regulates hepatic stem cell differentiation.
METHODS
A rat model of liver cirrhosis was established via subcutaneous injection of carbon tetrachloride (CCl4) for 8 wk. From the beginning of the ninth week, the rats received 2-acetylaminofluorene (2-AAF) by oral gavage and a DLK-1+ fetal liver stem/progenitor cell (FLSPC) transplant or an FLSPC transplant in combination with YGJ treatment for 4 wk. In vitro, lipopolysaccharide (LPS)-activated macrophages were co-cultured with WB-F344 cells, and the differentiation of WB-F344 cells was observed in the presence and absence of YGJ treatment.
RESULTS
FLSPC transplantation improved liver function and histopathology, and inhibited the activation of the non-canonical Wnt signaling pathway, while activating the canonical Wnt signaling pathway. YGJ enhanced the therapeutic effects of FLSPCs and also promoted the liver regeneration differentiation of FLSPCs into hepatocytes. In vitro, LPS-activated macrophages promoted the differentiation of WB-F344 cells into myofibroblasts, and the canonical Wnt signaling was inhibited while the non-canonical Wnt signaling was activated in WB-F344 cells. YGJ suppressed the activation of macrophages and then inhibited non-canonical Wnt signaling and promoted canonical Wnt signaling.
CONCLUSION
YGJ enhances FLSPC-mediated repair of liver cirrhosis through regulation of macrophage activation state, and YGJ in combination with stem cell transplantation may be a suitable treatment for end-stage liver cirrhosis.
Core tip: Stem cells play an important role in the treatment of end-stage liver cirrhosis, but details concerning their differentiation are still controversial. Our previous studies have indicated that Yiguanjian decoction (YGJ) has an anti-hepatic fibrosis effect. However, it remains unclear whether YGJ regulates stem cell differentiation. In this work, we found that YGJ may enhance fetal liver stem/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state in cirrhosis, suggesting that YGJ in combination with stem cell transplantation may be a suitable treatment for end-stage liver cirrhosis.
