ArticleHepatology (Baltimore, Md.)2017
MicroRNA 181b-3p and its target importin α5 regulate toll-like receptor 4 signaling in Kupffer cells and liver injury in mice in response to ethanol.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Past, Present, and Future Therapies for Alcohol-associated Hepatitis.Clinical therapeutics · 2023Pooled it
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- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
- Hyaluronic Acid in Liver Fibrosis: Role in Inflammation, Tissue Remodeling, and Disease Progression.International journal of molecular sciences · 2025Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD.Journal of advanced research · 2025Review
- Non-coding RNAs in alcohol-associated liver disease.Liver research (Beijing, China) · 2025Review
- 35k Da specific-sized hyaluronan ameliorates high-fat diet-induced liver injury in murine model of moderate obesity.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Alcohol-associated liver disease: Natural history, management and novel targeted therapies.Clinical and molecular hepatology · 2025Review
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- Alcohol-related liver disease.Gastroenterology report · 2025Review
- Network-Based Bioinformatics Highlights Broad Importance of Human Milk Hyaluronan.International journal of molecular sciences · 2024Article
- Dual peroxisome proliferator-activated receptor α/δ agonists: Hope for the treatment of alcohol-associated liver disease?World journal of gastroenterology · 2024Article
- Role of immune cell interactions in alcohol-associated liver diseases.Liver research (Beijing, China) · 2024Review
- MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?Cancers · 2023Review
- Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities.Pharmacology & therapeutics · 2023Review
- Karyopherin Subunit Alpha 1 Enhances the Malignant Behaviors of Colon Cancer Cells via Promoting Nuclear Factor-κB p65 Nuclear Translocation.Digestive diseases and sciences · 2023Article
- Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.Annual review of pathology · 2023Review
- miR-505-5p alleviates acute rejection of liver transplantation by inhibiting Myd88 and inducing M2 polarizationof Kupffer cells.Acta biochimica et biophysica Sinica · 2022Article
- Epigenetics of alcohol-related liver diseases.JHEP reports : innovation in hepatology · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Increased inflammatory signaling by Kupffer cells contributes to alcoholic liver disease (ALD). Here we investigated the impact of small, specific-sized hyaluronic acid of 35 kD (HA35) on ethanol-induced sensitization of Kupffer cells, as well as ethanol-induced liver injury in mice. Unbiased analysis of microRNA (miRNA) expression in Kupffer cells identified miRNAs regulated by both ethanol and HA35. Toll-like receptor 4 (TLR4)-mediated signaling was assessed in primary cultures of Kupffer cells from ethanol- and pair-fed rats after treatment with HA35. Female C57BL6/J mice were fed ethanol or pair-fed control diets and treated or not with HA35. TLR4 signaling was increased in Kupffer cells by ethanol; this sensitization was normalized by ex vivo treatment with HA35. Next generation sequencing of Kupffer cell miRNA identified miRNA 181b-3p (miR181b-3p) as sensitive to both ethanol and HA35. Importin α5, a protein involved in p65 translocation to the nucleus, was identified as a target of miR181b-3p; importin α5 protein was increased in Kupffer cells from ethanol-fed rats, but decreased by HA35 treatment. Overexpression of miR181b-3p decreased importin α5 expression and normalized lipopolysaccharide-stimulated tumor necrosis factor α expression in Kupffer cells from ethanol-fed rats. In a mouse model of ALD, ethanol feeding decreased miR181b-3p in liver and increased expression of importin α5 in nonparenchymal cells. Treatment with HA35 normalized these changes and also protected mice from ethanol-induced liver and intestinal injury.
conclusionmiR181b-3p is dynamically regulated in Kupffer cells and mouse liver in response to ethanol and treatment with HA35. miR181b-3p modulates expression of importin α5 and sensitivity of TLR4-mediated signaling. This study identifies a miR181b-3p-importin α5 axis in regulating inflammatory signaling pathways in hepatic macrophages. (Hepatology 2017;66:602-615).
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