ArticleWorld journal of gastroenterology2015
Inhibition of sphingosine kinase 1 ameliorates acute liver failure by reducing high-mobility group box 1 cytoplasmic translocation in liver cells.
Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Sphk1 regulates HMGB1 via HDAC4 and mediates epithelial pyroptosis in allergic rhinitis.The World Allergy Organization journal · 2024Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model.Frontiers in pharmacology · 2022Article
- Deletion or inhibition of SphK1 mitigates fulminant hepatic failure by suppressing TNFα-dependent inflammation and apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Sphingosine kinase 1 regulates HMGB1 translocation by directly interacting with calcium/calmodulin protein kinase II-δ in sepsis-associated liver injury.Cell death & disease · 2020Article
- Generation of mice with hepatocyte-specific conditional deletion of sphingosine kinase 1.Transgenic research · 2020Article
- DAMPs and sterile inflammation in drug hepatotoxicity.Hepatology international · 2019Review
- Sphingosine kinase and sphingosine-1-phosphate in liver pathobiology.Critical reviews in biochemistry and molecular biology · 2017Review
- HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure.Mediators of inflammation · 2017Review
- C5a/C5aR pathway is essential for up-regulating SphK1 expression through p38-MAPK activation in acute liver failure.World journal of gastroenterology · 2016Article
- Sphingosine kinase 1 inhibition improves lipopolysaccharide/D-galactosamine-induced acute liver failure by inhibiting mitogen-activated protein kinases pathway.United European gastroenterology journal · 2016Article
- The role of the sphingosine axis in immune regulation: A dichotomy in the anti-inflammatory effects between sphingosine kinase 1 and sphingosine kinase 2-dependent pathways.International journal of immunopathology and pharmacologyArticle
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo determine the therapeutic potential of sphingosine kinase 1 (Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure (ALF).
methodsBalb/c mice were randomly assigned to different groups, with ALF induced by intraperitoneal injection of D-GaIN (600 mg/kg) and LPS (10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells (PBMCs) was analyzed by Western blot.
resultsThe expression of Sphk1 in liver tissue and PBMCs was upregulated in GalN/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells, the resident macrophages of the liver. The survival rates of mice in the N,N-dimethylsphingosine (DMS, a specific inhibitor of SphK1) treatment group were significantly higher than that of the control group (P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6, 12, and 24 h compared with that of the control group (P < 0.01 for all). Serum HMGB1 levels at 6, 12, and 24 h, as well as serum TNF-α, IL-6, and IL-1β levels at 12 h, were significantly lower in the DMS treatment group than in the control group (P < 0.01 for all). Furthermore, hepatic inflammation, necrosis, and HMGB1 cytoplasm translocation in liver cells were significantly decreased in the DMS treatment group compared to the control group (43.72% ± 5.51% vs 3.57% ± 0.83%, χ(2) = 12.81, P < 0.01).
conclusionInhibition of SphK1 ameliorates ALF by reducing HMGB1 cytoplasmic translocation in liver cells, and so might be a potential therapeutic strategy for this disease.
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