ArticleJournal of cellular and molecular medicine2018
CXCL6-EGFR-induced Kupffer cells secrete TGF-β1 promoting hepatic stellate cell activation via the SMAD2/BRD4/C-MYC/EZH2 pathway in liver fibrosis.
Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Conserved hepatic RNA signatures across multiple cohorts reveal novel mechanistic clues for advanced fibrosis in human MASLD.Hepatology communications · 2026Pooled it
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- Uncovering potentially targetable genes in liver fibrosis via bioinformatics and experimental validation.Scientific reports · 2026Article
- Loganin Ameliorates Cholestatic Liver Fibrosis by Inhibiting Hepatic Stellate Cell Autophagy and Activation Through EGFR Signaling.Mediators of inflammation · 2026Article
- Comprehensive analysis of the TGF-β signaling pathway: molecular mechanisms, disease drivers, and frontiers in clinical translation.Frontiers in immunology · 2026Review
- From support to homeostatic licensing: the bidirectional fibroblast-macrophage circuit and its central role in tissue homeostasis and fibrosis.Frontiers in immunology · 2026Review
- Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025Review
- Single-cell transcription reveals hepatocyte-to-cholangiocyte reprogramming and biliary gene profile in biliary atresia.Hepatology communications · 2025Article
- Diagnostic and clinical relevance of targeted metabolomic analysis of serum bile acid profiles in acute pancreatitis.BMC gastroenterology · 2025Article
- Dynamic crosstalk between HSCs and liver microenvironment: multicellular interactions in the regulation of liver fibrosis.Frontiers in cell and developmental biology · 2025Review
- Integrated machine learning and single-cell RNA sequencing reveal COL4A2 and CXCL6 as oxidative stress-associated biomarkers in periodontitis.Frontiers in immunology · 2025Article
- New insights into combined immunotherapy for hepatocellular carcinoma associated with liver cirrhosis.Frontiers in immunology · 2025Review
- Proteomic Characterization of Corneal Epithelial and Stromal Cell-Derived Extracellular Vesicles.International journal of molecular sciences · 2024Article
- BRD4: an effective target for organ fibrosis.Biomarker research · 2024Review
- Inhibition of CK2 Diminishes Fibrotic Scar Formation and Improves Outcomes After Ischemic Stroke via Reducing BRD4 Phosphorylation.Neurochemical research · 2024Article
- A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage.iScience · 2024Article
- A detailed overview of quercetin: implications for cell death and liver fibrosis mechanisms.Frontiers in pharmacology · 2024Review
- The role of macrophages in liver fibrosis: composition, heterogeneity, and therapeutic strategies.Frontiers in immunology · 2024Review
- Integrated Bioinformatics and Validation RevealBiomolecules · 2023Article
- A narrative review: CXC chemokines influence immune surveillance in obesity and obesity-related diseases: Type 2 diabetes and nonalcoholic fatty liver disease.Reviews in endocrine & metabolic disorders · 2023Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver fibrosis is the excessive accumulation of extracellular matrix proteins in response to the inflammatory response that accompanies tissue injury, which at an advanced stage can lead to cirrhosis and even liver failure. This study investigated the role of the CXC chemokine CXCL6 (GCP-2) in liver fibrosis. The expression of CXCL6 was found to be elevated in the serum and liver tissue of high stage liver fibrosis patients. Furthermore, treatment with CXCL6 (100 ng/mL) stimulated the phosphorylation of EGFR and the expression of TGF-β in cultured Kupffer cells (KCs). Although treatment with CXCL6 directly did not activate the hepatic stellate cell (HSC) line, HSC-T6, HSCs cultured with media taken from KCs treated with CXCL6 or TGF-β showed increased expression of α-SMA, a marker of HSC activation. CXCL6 was shown to function via the SMAD2/BRD4/C-MYC/EZH2 pathway by enhancing the SMAD3-BRD4 interaction and promoting direct binding of BRD4 to the C-MYC promoter and CMY-C to the EZH2 promoter, thereby inducing profibrogenic gene expression in HSCs, leading to activation and transdifferentiation into fibrogenic myofibroblasts. These findings were confirmed in a mouse model of CCl
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