ArticleCell research2015
An HNF1α-regulated feedback circuit modulates hepatic fibrogenesis via the crosstalk between hepatocytes and hepatic stellate cells.
Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 82 citations in OpenAlex.
- [Novel targets and drugs for the treatment of portal hypertension in liver cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Hepatocyte-Derived S100A4/A6/A10/A11 Proteins Promote Liver Fibrosis by Direct and Indirect Activation of HSCs.Inflammation · 2026Article
- Multi-omics profiling reveals divergent biology and liver microenvironment in HCC of metastatic and de novo origin.Molecular cancer · 2026Article
- SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells.PLoS pathogens · 2026Article
- Integrated transcriptome and proteome analyses unveil cytoskeletal alterations in an endothelial model of monogenic diabetes.Genome medicine · 2026Article
- Extracellular Vesicles in Liver Fibrosis: Pathogenic Messengers, Diagnostic Biomarkers, and Therapeutic Nanovectors.Pharmaceutics · 2026Review
- Quantitative systems toxicology approach that integrates PBPK and core hepatic metabolism: a case study with valproic acid.Frontiers in pharmacology · 2026Article
- Review
- Western Diet Induces Changes in Gene Expression in Multiple Tissues During Early Insulin Resistance and Glucose Intolerance in Male C57BL/6 Mice.Current issues in molecular biology · 2025Article
- Determining gene specificity from multivariate single-cell RNA sequencing data.bioRxiv : the preprint server for biology · 2025Article
- SAMHD1 promotes SARS-CoV-2 infection by enhancing HNF1-dependent ACE2 expression in lung epithelial cells.bioRxiv : the preprint server for biology · 2025Article
- Unraveling the Regulatory Impact of LncRNA Hnf1aos1 on Hepatic Homeostasis in Mice.Non-coding RNA · 2025Article
- NLRP3 inflammasome inhibition decreasesInfection and immunity · 2024Article
- Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.Cell death & disease · 2024Article
- Pro-Inflammatory and Anti-Inflammatory Interleukins in Infectious Diseases: A Comprehensive Review.Tropical medicine and infectious disease · 2024Review
- The METTL3/m6A Reader Protein YTHDF1 Regulates Endothelial Cell Pyroptosis by Enhancing NLRP3 Expression to Affect Soft Tissue Injury.Journal of inflammation research · 2024Article
- Three-dimensional molecular architecture of mouse organogenesis.Nature communications · 2023Article
- Hepatocyte nuclear factor 1A suppresses innate immune response by inducing degradation of TBK1 to inhibit steatohepatitis.Genes & diseases · 2023Article
- Roles of protein tyrosine phosphatases in hepatocellular carcinoma progression (Review).Oncology reports · 2023Review
- Repair of Limb Ischemia Is Dependent on Hematopoietic Stem Cell Specific-SHP-1 Regulation of TGF-β1.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocytes are critical for the maintenance of liver homeostasis, but its involvement in hepatic fibrogenesis remains elusive. Hepatocyte nuclear factor 1α (HNF1α) is a liver-enriched transcription factor that plays a key role in hepatocyte function. Our previous study revealed a significant inhibitory effect of HNF1α on hepatocellular carcinoma. In this study, we report that the expression of HNF1α is significantly repressed in both human and rat fibrotic liver. Knockdown of HNF1α in the liver significantly aggravates hepatic fibrogenesis in either dimethylnitrosamine (DMN) or bile duct ligation (BDL) model in rats. In contrast, forced expression of HNF1α markedly alleviates hepatic fibrosis. HNF1α regulates the transcriptional expression of SH2 domain-containing phosphatase-1 (SHP-1) via directly binding to SHP-1 promoter in hepatocytes. Inhibition of SHP-1 expression abrogates the anti-fibrotic effect of HNF1α in DMN-treated rats. Moreover, HNF1α repression in primary hepatocytes leads to the activation of NF-κB and JAK/STAT pathways and initiates an inflammatory feedback circuit consisting of HNF1α, SHP-1, STAT3, p65, miR-21 and miR-146a, which sustains the deregulation of HNF1α in hepatocytes. More interestingly, a coordinated crosstalk between hepatocytes and hepatic stellate cells (HSCs) participates in this positive feedback circuit and facilitates the progression of hepatocellular damage. Our findings demonstrate that impaired hepatocytes play an active role in hepatic fibrogenesis. Early intervention of HNF1α-regulated inflammatory feedback loop in hepatocytes may have beneficial effects in the treatment of chronic liver diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.