ArticleExperimental and molecular pathology2014
TLR3/4 signaling is mediated via the NFκB-CXCR4/7 pathway in human alcoholic hepatitis and non-alcoholic steatohepatitis which formed Mallory-Denk bodies.
Article in Experimental and molecular pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Sterile inflammation in MASH: emerging role of extracellular RNA and therapeutic strategies.npj metabolic health and disease · 2025Review
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Extracellular RNA mediates iron-induced toxicity and inflammatory signalling in hepatic cells.Toxicology reports · 2025Article
- Research progress on the roles of complement in liver injury.World journal of hepatology · 2025Review
- Article
- Regulatory Networks, Management Approaches, and Emerging Treatments of Nonalcoholic Fatty Liver Disease.Canadian journal of gastroenterology & hepatology · 2022Review
- Emerging Importance of Chemokine Receptor CXCR4 and Its Ligand in Liver Disease.Frontiers in cell and developmental biology · 2021Review
- Toll-Like Receptors Recognize Intestinal Microbes in Liver Cirrhosis.Frontiers in immunology · 2021Review
- Roles of the complement system in alcohol-induced liver disease.Clinical and molecular hepatology · 2020Review
- The Role of FAT10 in Alcoholic Hepatitis Pathogenesis.Biomedicines · 2020Review
- Atorvastatin promotes AMPK signaling to protect against high fat diet-induced non-alcoholic fatty liver in golden hamsters.Experimental and therapeutic medicine · 2020Article
- Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation.Frontiers in immunology · 2020Article
- Tanshinone IIA ameliorates non-alcoholic fatty liver disease through targeting peroxisome proliferator-activated receptor gamma and toll-like receptor 4.The Journal of international medical research · 2019Article
- Different roles of FAT10, FOXO1, and ADRA2A in hepatocellular carcinoma tumorigenesis in patients with alcoholic steatohepatitis (ASH) vs non-alcoholic steatohepatitis (NASH).Experimental and molecular pathology · 2018Article
- Troxerutin Protects Kidney Tissue against BDE-47-Induced Inflammatory Damage through CXCR4-TXNIP/NLRP3 Signaling.Oxidative medicine and cellular longevity · 2018Article
- Berberine ameliorates non-alcoholic steatohepatitis in ApoEExperimental and therapeutic medicine · 2017Article
- The role of Tec kinase signaling pathways in the development of Mallory Denk Bodies in balloon cells in alcoholic hepatitis.Experimental and molecular pathology · 2017Article
- [Research advances in the pathogenesis of non-alcoholic fatty liver disease-associated liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2017Review
- Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?World journal of gastroenterology · 2016Article
- Aberrant modulation of the BRCA1 and G1/S cell cycle pathways in alcoholic hepatitis patients with Mallory Denk Bodies revealed by RNA sequencing.Oncotarget · 2015Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Activation of Toll-like receptor (TLR) signaling which stimulates inflammatory and proliferative pathways is the key element in the pathogenesis of Mallory-Denk bodies (MDBs) in mice fed DDC. However, little is known as to how TLR signaling is regulated in MDB formation during chronic liver disease development. The first systematic study of TLR signaling pathway transcript regulation in human archived formalin-fixed, paraffin-embedded (FFPE) liver biopsies with MDB formation is presented here. When compared to the activation of Toll-like signaling in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH) patients, striking similarities and obvious differences were observed. Similar TLRs (TLR3 and TLR4, etc.), TLR downstream adaptors (MyD88 and TRIF, etc.) and transcript factors (NFκB and IRF7, etc.) were all upregulated in the patients' livers. MyD88, TLR3 and TLR4 were significantly induced in the livers of AH and NASH compared to normal subjects, while TRIF and IRF7 mRNA were only slightly upregulated in AH patients. This is a different pathway from the induction of the TLR4-MyD88-independent pathway in the AH and NASH patients with MDBs present. Importantly, chemokine receptor 4 and 7 (CXCR4/7) mRNAs were found to be induced in the patients livers in FAT10 positive hepatocytes. The CXCR7 pathway was significantly upregulated in patients with AH and the CXCR4 was markedly upregulated in patients with NASH, indicating that CXCR4/7 is crucial in liver MDB formation. This data constitutes the first demonstration of the upregulation of the MyD88-dependent TLR4/NFκB pathway in AH and NASH where MDBs formed, via the NFκB-CXCR4/7 pathway, and provides further insight into the mechanism of MDB formation in human liver diseases.
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