ArticleJournal of toxicologic pathology2022
LPS-TLR4/MD-2-TNF-α signaling mediates alcohol-induced liver fibrosis in rats.
Article in Journal of toxicologic pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Mapping the knowledge domains of literature on hepatocellular carcinoma and liver failure: a bibliometric approach.Frontiers in oncology · 2025Pooled it
- Contribution of p38 MAPK in liver fibrosis: An overview of mechanisms, signaling pathways, and therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Toll-like receptor 2 modulates age-associated insulitis and fibrotic remodeling of Langerhans islets.Immunity & ageing : I & A · 2026Article
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- 3-carbamoyl proxyl nitroxide attenuates CClScientific reports · 2026Article
- Targeting DNA fragment extrusion: a new therapeutic avenue for CClMolecular biology reports · 2026Article
- Nanomedicine-Driven Modulation of Signaling Pathways in Hepatic Fibrosis.International journal of nanomedicine · 2026Review
- Comparative Study of DTMUV and LPS on Duck Liver Disease.Veterinary sciences · 2025Article
- Present and Future Perspectives in the Treatment of Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction.World journal of biological chemistry · 2025Review
- Advances in Understanding Lipopolysaccharide-Mediated Hepatitis: Mechanisms and Pathological Features.Current issues in molecular biology · 2025Review
- Gut‑liver axis in liver disease: From basic science to clinical treatment (Review).Molecular medicine reports · 2025Review
- Decoding the heterogeneity of liver-resident macrophages in chronic liver diseases: therapeutic responses to immunomodulatory strategies.Frontiers in pharmacology · 2025Review
- Molecular Mechanisms of Fibrosis in Cholestatic Liver Diseases and Regenerative Medicine-Based Therapies.Cells · 2024Review
- Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils.Cellular and molecular gastroenterology and hepatology · 2024Review
- Alcohol-induced liver injury in signalling pathways and curcumin's therapeutic potential.Toxicology reports · 2023Review
- Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.International journal of molecular sciences · 2023Review
- Intestinal Microbiotas and Alcoholic Hepatitis: Pathogenesis and Therapeutic Value.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)-tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2-TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin-eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2-TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2-TNF-α signaling pathway.
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Registered trials
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