PMID- 30671485
OWN - NLM
STAT- MEDLINE
DCOM- 20190408
LR  - 20200225
IS  - 2314-7156 (Electronic)
IS  - 2314-8861 (Print)
IS  - 2314-7156 (Linking)
VI  - 2018
DP  - 2018
TI  - M1-Polarized Macrophages Promote Self-Renewing Phenotype of Hepatic Progenitor 
      Cells with Jagged1-Notch Signalling Involved: Relevance in Primary Sclerosing 
      Cholangitis.
PG  - 4807145
LID - 10.1155/2018/4807145 [doi]
LID - 4807145
AB  - The immunologic interaction between parenchyma cells and encircling inflammatory 
      cells is thought to be the most important mechanism of biliary damage and repair 
      in primary sclerosing cholangitis (PSC). Monocytes/macrophages as master 
      regulators of hepatic inflammation have been demonstrated to contribute to PSC 
      pathogenesis. Macrophages coordinate with liver regeneration, and multiple 
      phenotypes have been identified with diverse expressions of surface proteins and 
      cytokine productions. We analyzed the expression of Notch ligand Jagged1 in 
      polarized macrophages and investigated the relevance of Notch signalling 
      activation in liver regeneration. M1 or M2 macrophages were generated from mouse 
      bone marrow-derived macrophages (BMDMs) by classical or alternative activation, 
      respectively. Then, the expression levels of Jagged1 (Jag1) of each phenotype 
      were measured. The effects of polarized BMDMs on the expression of hepatic 
      progenitor cell- (HPC-) specific markers and hairy and enhancer of split-1 (HES1) 
      in HPCs in coculture were also analyzed. Monocyte-macrophage and Notch 
      signalling-associated gene signatures were evaluated in the GEO database (access 
      ID: GSE61260) by gene set enrichment analysis (GSEA). M1 macrophages were found 
      associated with elevated Jag1 expression, which increased the fraction of HPC 
      with self-renewing phenotypes (CD326(+)CD44(+) or CD324(+)CD44(+)) and HES1 
      expression level in cocultured HPC. Blocking Jagged1 by siRNA or antibody in the 
      coculture system attenuates HPC self-renewing phenotypes as well as HES1 
      expression in HPC. GSEA data show that macrophage activation and Notch 
      signalling-associated gene signatures are enriched in PSC patients. These 
      findings suggest that M1 macrophages promote an HPC self-renewing phenotype which 
      is associated with Notch signalling activation within HPC. In the liver of PSC 
      patients, the prevalence of activated macrophages, with M1 polarized accounting 
      for the main part, is associated with increment of Notch signalling and 
      enhancement of HPC self-renewal.
FAU - Li, Heli
AU  - Li H
AD  - Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
AD  - Department of Immunology, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
FAU - Sun, Shiran
AU  - Sun S
AD  - Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Lei, Qing
AU  - Lei Q
AD  - Department of Immunology, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
FAU - Lei, Ping
AU  - Lei P
AD  - Department of Immunology, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
FAU - Cai, Xiong
AU  - Cai X
AUID- ORCID: 0000-0003-2034-9130
AD  - Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Wan, Chidan
AU  - Wan C
AD  - Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Shen, Guanxin
AU  - Shen G
AD  - Department of Immunology, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
LA  - eng
PT  - Journal Article
DEP - 20181224
PL  - Egypt
TA  - J Immunol Res
JT  - Journal of immunology research
JID - 101627166
RN  - 0 (Cytokines)
RN  - 0 (Jagged-1 Protein)
RN  - 0 (Receptors, Notch)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Self Renewal
MH  - Cells, Cultured
MH  - Cholangitis, Sclerosing/*immunology
MH  - Cytokines/metabolism
MH  - Female
MH  - Green Fluorescent Proteins/genetics
MH  - Humans
MH  - Jagged-1 Protein/metabolism
MH  - Liver/*physiology
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Phenotype
MH  - Pregnancy
MH  - Receptors, Notch/metabolism
MH  - Signal Transduction
MH  - Th1 Cells/immunology
PMC - PMC6323443
EDAT- 2019/01/24 06:00
MHDA- 2019/04/09 06:00
PMCR- 2018/12/24
CRDT- 2019/01/24 06:00
PHST- 2018/06/08 00:00 [received]
PHST- 2018/09/28 00:00 [revised]
PHST- 2018/10/22 00:00 [accepted]
PHST- 2019/01/24 06:00 [entrez]
PHST- 2019/01/24 06:00 [pubmed]
PHST- 2019/04/09 06:00 [medline]
PHST- 2018/12/24 00:00 [pmc-release]
AID - 10.1155/2018/4807145 [doi]
PST - epublish
SO  - J Immunol Res. 2018 Dec 24;2018:4807145. doi: 10.1155/2018/4807145. eCollection 
      2018.