M1-Polarized Macrophages Promote Self-Renewing Phenotype of Hepatic Progenitor Cells with Jagged1-Notch Signalling Involved: Relevance in Primary Sclerosing Cholangitis
Joint Authors
Lei, Qing
Sun, Shiran
Lei, Ping
Cai, Xiong
Shen, Guanxin
Li, Heli
Wan, Chidan
Source
Journal of Immunology Research
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-12-24
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Li, Heli& Sun, Shiran& Lei, Qing& Lei, Ping& Cai, Xiong& Wan, Chidan…[et al.]. 2018. M1-Polarized Macrophages Promote Self-Renewing Phenotype of Hepatic Progenitor Cells with Jagged1-Notch Signalling Involved: Relevance in Primary Sclerosing Cholangitis. Journal of Immunology Research،Vol. 2018, no. 2018, pp.1-12.
https://search.emarefa.net/detail/BIM-1192407
Modern Language Association (MLA)
Li, Heli…[et al.]. M1-Polarized Macrophages Promote Self-Renewing Phenotype of Hepatic Progenitor Cells with Jagged1-Notch Signalling Involved: Relevance in Primary Sclerosing Cholangitis. Journal of Immunology Research No. 2018 (2018), pp.1-12.
https://search.emarefa.net/detail/BIM-1192407
American Medical Association (AMA)
Li, Heli& Sun, Shiran& Lei, Qing& Lei, Ping& Cai, Xiong& Wan, Chidan…[et al.]. M1-Polarized Macrophages Promote Self-Renewing Phenotype of Hepatic Progenitor Cells with Jagged1-Notch Signalling Involved: Relevance in Primary Sclerosing Cholangitis. Journal of Immunology Research. 2018. Vol. 2018, no. 2018, pp.1-12.
https://search.emarefa.net/detail/BIM-1192407
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192407