ArticleCell death & disease2021
Targeting SYK of monocyte-derived macrophages regulates liver fibrosis via crosstalking with Erk/Hif1α and remodeling liver inflammatory environment.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- A Novel PLGA-based nano-adjuvant augments mucosal and systemic immunity in chicks through intestinal targeting and IgA production.Poultry science · 2026Article
- Sustained monocyte activation by persistent challenges with either oxLDL or free cholesterol and underlying mechanisms.ImmunoHorizons · 2026Article
- HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2-Dectin-1/ SYK mediated ROS and inflammatory responses.Scientific reports · 2025Article
- Syk inhibitor attenuates lupus in FcγRIIbCell death discovery · 2025Article
- Review
- SYK promotes the formation of neutrophil extracellular traps by inducing PKM2 nuclear translocation and promoting STAT3 phosphorylation to exacerbate hepatic ischemia-reperfusion injury and tumor recurrence.Molecular medicine (Cambridge, Mass.) · 2024Article
- The complex role of immune cells in antigen presentation and regulation of T-cell responses in hepatocellular carcinoma: progress, challenges, and future directions.Frontiers in immunology · 2024Review
- Repurposing Niclosamide as a Therapeutic Drug against Acute Liver Failure by Suppressing Ferroptosis.Pharmaceutics · 2023Article
- Hepatocyte SGK1 activated by hepatic ischemia-reperfusion promotes the recurrence of liver metastasis via IL-6/STAT3.Journal of translational medicine · 2023Article
- Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy.Frontiers in pharmacology · 2023Article
- Theabrownin ameliorates liver inflammation, oxidative stress, and fibrosis in MCD diet-fed C57BL/6J mice.Frontiers in endocrinology · 2023Article
- Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation.Frontiers in molecular biosciences · 2023Article
- Article
- The spleen tyrosine kinase (SYK): A crucial therapeutic target for diverse liver diseases.Heliyon · 2022Review
- Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver fibrosis is a danger signal indicating a huge risk of liver cancer occurrence, but there is still no effective clinical means to regulate the progress of liver fibrosis. Although a variety of drugs targeting SYK have been developed for tumors and autoimmune diseases, the mechanism and specific efficacy of SYK's role in liver fibrosis are not yet clear. Our studies based on chronic CCL4, bile duct ligation, and subacute TAA mouse models show that SYK in monocyte-derived macrophages (MoMFs) is fully dependent on phosphorylation of Erk to up-regulate the expression of Hif1α, thereby forming the crosstalk with SYK to drive liver fibrosis progress. We have evaluated the ability of the small molecule SYK inhibitor GS9973 in a variety of models. Contrary to previous impressions, high-frequency administration of GS9973 will aggravate CCL4-induced liver fibrosis, which is especially unsuitable for patients with cholestasis whose clinical features are bile duct obstruction. In addition, we found that inhibition of MoMFs SYK impairs the expression of CXCL1, on one hand, it reduces the recruitment of CD11bhiLy6Chi inflammatory cells, and on the other hand, it promotes the phenotype cross-dress process of pro-resolution MoMFs, thereby remodeling the chronic inflammatory environment of the fibrotic liver. Our further findings indicate that on the basis of the administration of CCR2/CCR5 dual inhibitor Cenicriviroc, further inhibiting MoMFs SYK may give patients with fibrosis additional benefits.
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