PMID- 37408817
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2310-8819 (Electronic)
IS  - 2225-0719 (Print)
IS  - 2225-0719 (Linking)
VI  - 11
IP  - 4
DP  - 2023 Aug 28
TI  - IGF2-NR4A2 Signaling Regulates Macrophage Subtypes to Attenuate Liver Cirrhosis.
PG  - 787-799
LID - 10.14218/JCTH.2022.00392 [doi]
AB  - BACKGROUND AND AIMS: Liver cirrhosis can lead to liver failure and eventually 
      death. Macrophages are the main contributors to cirrhosis and have a 
      bidirectional role in regulating matrix deposition and degradation. 
      Macrophage-based cell therapy has been developed as an alternative to liver 
      transplantation. However, there is insufficient evidence regarding its safety and 
      efficacy. In this study, we aimed to explore the effect of combining insulin-like 
      growth factor 2 (IGF2) with bone marrow-derived macrophages (BMDMs) to treat mice 
      with liver cirrhosis. METHODS: We assessed liver inflammation, fibrosis 
      regression, liver function, and liver regeneration in mice with CCl(4)-induced 
      cirrhosis and treated with BMDM only or IGF2 + BMDM. We performed in vitro 
      experiments in which activated hepatic stellate cells (HSCs) were co-cultured 
      with macrophages in the presence or absence of IGF2. The polarity of macrophages 
      and the degree of inhibition of HSCs were examined. The effect of IGF2 on 
      macrophages was also verified by the overexpression of IGF2. RESULTS: Combining 
      IGF2 with BMDM reduced liver inflammation and fibrosis and increased hepatocyte 
      proliferation. Combining IGF2 with BMDM was more effective than using BMDM alone. 
      In vitro experiments demonstrated that IGF2 inhibited HSCs activation by 
      upregulating NR4A2 to promote the anti-inflammatory macrophages phenotype. IGF2 
      also increased the synthesis of matrix metalloproteinases (MMPs) by macrophages, 
      which may explain why administering IGF2 combined with BMDM was more effective 
      than administering BMDM only. CONCLUSIONS: Our study provides a theoretical basis 
      for the future use of BMDM-based cell therapy to treat liver cirrhosis.
CI  - (c) 2023 Authors.
FAU - Yao, Lichao
AU  - Yao L
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Hu, Xue
AU  - Hu X
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Yuan, Mengqin
AU  - Yuan M
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Zhang, Qiuling
AU  - Zhang Q
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Liu, Pingji
AU  - Liu P
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Yang, Lian
AU  - Yang L
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, Hubei, China.
FAU - Dai, Kai
AU  - Dai K
AUID- ORCID: 0000-0001-7270-9965
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Jiang, Yingan
AU  - Jiang Y
AUID- ORCID: 0000-0003-4912-7494
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
LA  - eng
PT  - Journal Article
DEP - 20230131
PL  - United States
TA  - J Clin Transl Hepatol
JT  - Journal of clinical and translational hepatology
JID - 101649815
PMC - PMC10318280
OTO - NOTNLM
OT  - Cell therapy
OT  - Hepatic stellate cell
OT  - IGF2
OT  - Liver cirrhosis
OT  - Macrophage
COIS- The authors have no conflict of interests related to this publication.
EDAT- 2023/07/06 06:42
MHDA- 2023/07/06 06:43
PMCR- 2023/01/31
CRDT- 2023/07/06 04:08
PHST- 2022/08/11 00:00 [received]
PHST- 2022/10/18 00:00 [revised]
PHST- 2022/11/20 00:00 [accepted]
PHST- 2023/07/06 06:43 [medline]
PHST- 2023/07/06 06:42 [pubmed]
PHST- 2023/07/06 04:08 [entrez]
PHST- 2023/01/31 00:00 [pmc-release]
AID - JCTH.2022.00392 [pii]
AID - 10.14218/JCTH.2022.00392 [doi]
PST - ppublish
SO  - J Clin Transl Hepatol. 2023 Aug 28;11(4):787-799. doi: 10.14218/JCTH.2022.00392. 
      Epub 2023 Jan 31.