ArticleLaboratory investigation; a journal of technical methods and pathology2017
Spleen-derived lipocalin-2 in the portal vein regulates Kupffer cells activation and attenuates the development of liver fibrosis in mice.
Article in Laboratory investigation; a journal of technical methods and pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- The Spleen Promotes Liver Sinusoidal Endothelial Cell Angiogenesis by Stimulating the TGFβ/Smad2/3 Pathway Through GDF15.Journal of gastroenterology and hepatology · 2026Article
- Decoding the CHI3L1/IL-13Rα2 signaling nexus in MASH-fibrosis pathogenesis.Science advances · 2025Article
- Review
- [Research progress on the mechanistic role and constituents of hepatic macrophages during the occurrence and development of hepatic fibrosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Novel regulators of hepatic macrophages in liver fibrosis.Frontiers in immunology · 2025Review
- Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections.World journal of hepatology · 2024Review
- The mechanisms underlying alcohol-induced decreased splenic size: A network meta-analysis study.Alcohol, clinical & experimental research · 2024Article
- Combination treatment of mannose and GalNAc conjugated small interfering RNA protects against lethal Marburg virus infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Iron-accumulating splenocytes may exacerbate non-alcoholic steatohepatitis through the production of proinflammatory cytokines and reactive oxygen species.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Extrahepatic factors in hepatic immune regulation.Frontiers in immunology · 2022Review
- Effect of splenectomy on the outcomes in patients with cirrhosis receiving transjugular intrahepatic portosystemic shunt.Journal of gastroenterology and hepatology · 2021Article
- Review
- Splenectomy improves liver fibrosis via tumor necrosis factor superfamily 14 (LIGHT) through the JNK/TGF-β1 signaling pathway.Experimental & molecular medicine · 2021Article
- Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities.Cellular & molecular immunology · 2021Review
- Article
- Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis.Immunity & ageing : I & A · 2020Article
- Functions and regulation of lipocalin-2 in gut-origin sepsis: a narrative review.Critical care (London, England) · 2019Review
- Liver Macrophages: Old Dogmas and New Insights.Hepatology communications · 2019Review
- Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases.Frontiers in immunology · 2019Review
- Gut Microbiota's Relationship with Liver Disease and Role in Hepatoprotection by Dietary Natural Products and Probiotics.Nutrients · 2018Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver has an immune tolerance against gut-derived products from the portal vein (PV). A disruption of the gut-liver axis leads to liver injury and fibrosis. The spleen is connected to the PV and regulates immune functions. However, possible splenic effects on liver fibrosis development are unclear. Lipocalin-2 (Lcn2) is an antimicrobial protein that regulates macrophage activation. To clarify the role of the spleen in liver fibrosis development, we induced liver fibrosis in mice after splenectomy, and investigated liver fibrosis development. Liver fibrosis resulted in significantly increased splenic Lcn2 levels, but all other measured cytokine levels were unchanged. Splenectomized mice showed enhanced liver fibrosis and inflammation accompanied by significantly decreased Lcn2 levels in PV. Lipopolysaccharide-stimulated primary Kupffer cells, resident liver macrophages, which were treated with recombinant Lcn2 (rLcn2) produced less tumor necrosis factor-α and Ccl2 and the activation of hepatic stellate cells, the effector cells for collagen production in the liver, was suppressed by co-culture with rLcn2-treated Kupffer cells. In addition, the involvement of gut-derived products in splenectomized mice was evaluated by gut sterilization. Interestingly, gut sterilization blocked the effect of splenectomy on liver fibrosis development. In conclusion, spleen deficiency accelerated liver fibrosis development and decreased PV Lcn2 levels. The mechanism of splenic protection against liver fibrosis development may involve the splenic Lcn2, triggered by gut-derived products that enter the liver through the PV, regulates Kupffer cells activated by the gut-liver axis. Thus, the splenic Lcn2 may have an important role in regulating the immune tolerance of the liver in liver fibrosis development.
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