ArticleCell & bioscience2025
M1-BMDMs with Wnt5a deletion attenuate liver fibrosis by suppression of Wnt5a/Frizzled 2 axis in hepatic progenitors.
Article in Cell & bioscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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1 citing paper in PubMed.
- Wnt/β -catenin signalling shapes macrophage behaviour during injury and repair in the mouse submandibular gland.Scientific reports · 2026Article
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14 authors.
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Abstract
backgroundBone 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.
methodsFirst, Wnt5a protein expression was assessed in liver biopsy tissues from patients with hepatitis B-associated liver fibrosis. Second, cirrhosis was induced in rats using CCl4/2-AAF. In week 9, rats received intravenous injections of M1-BMDMs with Wnt5a knockdown (M1-BMDM Wnt5a−KD) or overexpression (M1-BMDM Wnt5a−OE); 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 frizzled 2 (Fzd2) knockdown (WB-F344 Fzd2−KD) or overexpression (WB-F344 Fzd2−OE) were cultured with conditioned medium from M1-BMDM Wnt5a−KD (CM Wnt5a−KD) or M1-BMDM Wnt5a−OE (CM Wnt5a−OE).
resultsIn patients with hepatitis B-related fibrosis, hepatic Wnt5a expression increased progressively with METAVIR fibrosis grade. In the rat cirrhosis model, M1-BMDMs Wnt5a−KD attenuated fibrosis, whereas M1-BMDMs Wnt5a−OE exacerbated it. Mechanistically, in vivo injection of M1-BMDMs Wnt5a−KD significantly inhibited HPCs differentiation into biliary epithelial cells (BECs), while M1-BMDM Wnt5a−OE promoted this differentiation. In vitro, CM Wnt5a−KD inhibited the differentiation of WB-F344 cells into BECs; this inhibition was potentiated by Fzd2 knockdown in WB-F344 cells but abrogated by Fzd2 overexpression. Conversely, under CM Wnt5a−OE conditions, WB-F344 Fzd2−OE cells exhibited increased cholangiocytic differentiation, an effect largely negated by Fzd2 knockdown.
conclusionsM1-BMDMs Wnt5a−KD demonstrated superior therapeutic efficacy against cirrhosis compared to unmodified M1-BMDMs. Wnt5a/Fzd2 signaling mediated the crosstalk between M1-BMDMs Wnt5a−KD and HPCs, revealing a novel therapeutic target for cirrhosis treatment.
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