ArticleGenes & diseases2023
Hepatocyte nuclear factor 1A suppresses innate immune response by inducing degradation of TBK1 to inhibit steatohepatitis.
Article in Genes & diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Cell Type-Specific Roles of TBK1 in Steatotic Liver Disease: Evidence for an Inflammatory TBK1Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Integrated transcriptome and proteome analyses unveil cytoskeletal alterations in an endothelial model of monogenic diabetes.Genome medicine · 2026Article
- Microbial exposure and host responses to infection reshape the disease trajectory of MASLD.Frontiers in cellular and infection microbiology · 2026Review
- Dynamic chromatin accessibility and transcriptional landscapes of porcine kidney cells during pseudorabies virus infection.Frontiers in immunology · 2026Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Targeting the Liver Serine Protease TMPRSS6 Ameliorates Steatosis and Attenuates Fibrosis in Experimental MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Dimethyl fumarate alleviate hepatic ischemia-reperfusion injury through suppressing cGAS-STING signaling.MedComm · 2025Article
- Temporal transcriptional profiling of host cells infected by a veterinary alphaherpesvirus using nanopore sequencing.Scientific reports · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Genomic and Transcriptomic Profile of HNF1A-Mutated Liver Adenomas Highlights Molecular Signature and Potential Therapeutic Implications.International journal of molecular sciences · 2024Article
- Blockade of the mitochondrial DNA release ameliorates hepatic ischemia-reperfusion injury through avoiding the activation of cGAS-Sting pathway.Journal of translational medicine · 2024Article
- The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop.Mechanisms of ageing and development · 2024Article
- TBK1 is paradoxical in tumor development: a focus on the pathway mediating IFN-I expression.Frontiers in immunology · 2024Review
- Integrative analysis of bulk and single-cell RNA sequencing data reveals distinct subtypes of MAFLD based on N1-methyladenosine regulator expression.Liver research (Beijing, China) · 2023Article
- HNF1A regulates the crosstalk between innate immune responses and MAFLD by mediating autophagic degradation of TBK1.Autophagy · 2023Article
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9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic steatohepatitis (NASH), a progressive form of non-alcoholic fatty liver disease (NAFLD), is characterised by chronic liver inflammation, which can further progress into complications such as liver cirrhosis and NASH-associated hepatocellular carcinoma (HCC) and therefore has become a growing health problem worldwide. The type I interferon (IFN) signaling pathway plays a pivotal role in chronic inflammation; however, the molecular mechanisms underlying NAFLD/NASH from the perspective of innate immune response has not yet been fully explored. In this study, we elucidated the mechanisms of how innate immune response modulates NAFLD/NASH pathogenesis, and demonstrated that hepatocyte nuclear factor-1alpha (HNF1A) was suppressed and the type I IFN production pathway was activated in liver tissues of patients with NAFLD/NASH. Further experiments suggested that HNF1A negatively regulates the TBK1-IRF3 signaling pathway by promoting autophagic degradation of phosphorylated-TBK1, which constrains IFN production, thereby inhibiting the activation of type I IFN signaling. Mechanistically, HNF1A interacts with the phagophore membrane protein LC3 through its LIR-docking sites, and mutations of LIRs (LIR2, LIR3, LIR4, and LIRs) block the HNF1A-LC3 interaction. In addition, HNF1A was identified not only as a novel autophagic cargo receptor but also to specifically induce K33-linked ubiquitin chains on TBK1 at Lys670, thereby resulting in autophagic degradation of TBK1. Collectively, our study illustrates the crucial function of the HNF1A-TBK1 signaling axis in NAFLD/NASH pathogenesis via cross-talk between autophagy and innate immunity.
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