Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Bone marrow-derived macrophages (BMDMs) regulate hepatic progenitor cells (HPCs) differentiation, potentially via the Wnt signaling pathway. While M1-polarized BMDMs (M1-BMDMs) exert anti-fibrotic effects in the liver, Wnt5a is implicated in fibrosis progression. The specific influence of Wnt5a levels within M1-BMDMs on HPCs fate and cirrhosis development remains unclear. This study aimed to elucidate the relationship between M1-BMDM-derived Wnt5a and HPCs differentiation during cirrhosis progression.
Methods: First, Wnt5a protein expression was assessed in liver biopsy tissues from patients with hepatitis B-associated liver fibrosis. Second, cirrhosis was induced in rats using CCl/2-AAF. In week 9, rats received intravenous injections of M1-BMDMs with Wnt5a knockdown (M1-BMDM ) or overexpression (M1-BMDM ); peripheral BMDMs recruitment was blocked using a CCR2 inhibitor. Fibrosis progression, ductular reaction (DR), and HPC differentiation were evaluated. In vitro, WB-F344 cells subjected to 2 (2) knockdown (WB-F344 ) or overexpression (WB-F344 ) were cultured with conditioned medium from M1-BMDM (CM ) or M1-BMDM (CM ).
Results: In patients with hepatitis B-related fibrosis, hepatic Wnt5a expression increased progressively with METAVIR fibrosis grade. In the rat cirrhosis model, M1-BMDMs attenuated fibrosis, whereas M1-BMDMs exacerbated it. Mechanistically, in vivo injection of M1-BMDMs significantly inhibited HPCs differentiation into biliary epithelial cells (BECs), while M1-BMDM promoted this differentiation. In vitro, CM inhibited the differentiation of WB-F344 cells into BECs; this inhibition was potentiated by knockdown in WB-F344 cells but abrogated by overexpression. Conversely, under CM conditions, WB-F344 cells exhibited increased cholangiocytic differentiation, an effect largely negated by knockdown.
Conclusions: M1-BMDMs demonstrated superior therapeutic efficacy against cirrhosis compared to unmodified M1-BMDMs. Wnt5a/Fzd2 signaling mediated the crosstalk between M1-BMDMs and HPCs, revealing a novel therapeutic target for cirrhosis treatment.
Supplementary Information: The online version contains supplementary material available at 10.1186/s13578-025-01467-x.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398029 | PMC |
| http://dx.doi.org/10.1186/s13578-025-01467-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
M1-BMDMs with Wnt5a deletion attenuate liver fibrosis by suppression of Wnt5a/Frizzled 2 axis in hepatic progenitors.
Cell Biosci
August 2025
Institute of Liver Diseases, Key Laboratory of Liver and Kidney Disease of the Ministry of Education, Clinical Key Laboratory of TCM of Shanghai, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai University of TCM, 528, Zhangheng Road, Pudong District, Shanghai,
Background: Bone marrow-derived macrophages (BMDMs) regulate hepatic progenitor cells (HPCs) differentiation, potentially via the Wnt signaling pathway. While M1-polarized BMDMs (M1-BMDMs) exert anti-fibrotic effects in the liver, Wnt5a is implicated in fibrosis progression. The specific influence of Wnt5a levels within M1-BMDMs on HPCs fate and cirrhosis development remains unclear.
View Article and Find Full Text PDFHepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.
Theranostics
April 2024
Institute of Liver diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Article Synopsis
- This study looks at how liver cells called hepatic progenitor cells (HPCs) react during liver damage and whether this helps the liver heal or makes it worse.
- The researchers found that when liver damage happens, HPCs can get more active and develop into another type of cell called cholangiocytes, which is linked to worsening liver fibrosis (scarring).
- They also discovered that a protein called Gli1 plays a big role in this process, and by reducing Gli1, they could decrease the damage and scarring in the liver.
The Wnt/β-catenin signaling pathway plays a role in drug-induced liver injury by regulating cytochrome P450 2E1 expression.
Toxicol Res
July 2023
Laboratory of Veterinary Toxicology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826 Republic of Korea.
Unlabelled: Drug-induced liver injury (DILI) is a major cause of acute liver failure and drug withdrawal. Cytochrome P450 (CYP) 2E1 is involved in the metabolism of several drugs, and can induce liver injury through the production of toxic metabolites and the generation of reactive oxygen species. This study aimed to elucidate the role of Wnt/β-catenin signaling in CYP2E1 regulation for drug-induced hepatotoxicity.
View Article and Find Full Text PDFLncRNA SNHG12 promotes proliferation and migration of hepatic progenitor cells via the Wnt/β-catenin pathway.
Adv Clin Exp Med
September 2023
Department of Nursing, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
Background: Hepatic progenitor cells (HPCs) play an important role in the treatment of chronic liver disease.
Objectives: To investigate the effect and mechanism of long noncoding RNAs/small nucleolar RNA host gene 12 (lncRNA SNHG12) on the proliferation and migration of the HPC cell line WB-F344.
Material And Methods: Hepatic progenitor cells were divided into a no-treatment group (sham), empty vector transfection of plasmid pcDNA3.
BM-MSCs overexpressing the Numb enhance the therapeutic effect on cholestatic liver fibrosis by inhibiting the ductular reaction.
Stem Cell Res Ther
March 2023
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Shanghai University of TCM, Key Laboratory of Liver and Kidney Disease of the Ministry of Education, Clinical Key Laboratory of TCM of Shanghai, 528, Zhangheng Road, Pudong Distric
Article Synopsis
- Cholestatic liver fibrosis (CLF) develops due to damage to bile ducts and involves the Notch signaling pathway, with reduced Numb protein potentially influencing disease progression.
- This study examined how manipulating the Numb gene in stem cells affected liver repair in rat models of CLF, revealing that Numb overexpression promoted healthy liver cell (hepatocyte) formation, while its knockdown led to harmful epithelial cell growth.
- The research suggests that enhancing Numb function could be a potential therapeutic strategy for treating CLF by guiding the differentiation of stem cells towards beneficial liver cell types.