ArticleHepatology (Baltimore, Md.)2014
E2F1 is a novel fibrogenic gene that regulates cholestatic liver fibrosis through the Egr-1/SHP/EID1 network.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 112 citations in OpenAlex.
- Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD.JCI insight · 2020Trial
- Leucyl tRNA synthetase ameliorates cholestatic liver injury by inhibiting integrated stress response in mice.Scientific reports · 2026Article
- Pilot Study on the Use of Rheology and Low Field Nmr to Characterize the Liver of Obese Patients Undergoing Metabolic and Bariatric Surgery.International journal of molecular sciences · 2026Article
- Proteomics reveals the key transcription-related factors mediating obstructive nephropathy in pediatric patients and mice.Renal failure · 2025Article
- Utility of the continuous spectrum formed by pathological states in characterizing disease properties.NPJ systems biology and applications · 2025Article
- Orphan Nuclear Receptors in Metabolic Dysfunction-associated Steatotic Liver Disease Development.Journal of clinical and translational hepatology · 2025Review
- The Non-Canonical ChREBPα Activity Suppresses the Activation of Hepatic Stellate Cells and Liver Fibrosis by Antagonizing TGF-β-E2F1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hotspots and trends in stem cell therapy for liver fibrosis and cirrhosis: A bibliometric analysis.World journal of hepatology · 2025Article
- Extracellular Vesicles from Mesenchymal Stem Cells: Potential as Therapeutics in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Biomedicines · 2024Review
- BiliQML: a supervised machine-learning model to quantify biliary forms from digitized whole slide liver histopathological images.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Blocking EGR1/TGF-β1 and CD44s/STAT3 Crosstalk Inhibits Peritoneal Metastasis of Gastric Cancer.International journal of biological sciences · 2024Article
- The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress.International journal of molecular sciences · 2023Review
- Nedd4L suppression in lung fibroblasts facilitates pathogenesis of lung fibrosis.Translational research : the journal of laboratory and clinical medicine · 2023Article
- E2F1 regulates miR-215-5p to aggravate paraquat-induced pulmonary fibrosis via repressing BMPR2 expression.Toxicology research · 2022Article
- Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver diseaseAdipocyte · 2022Article
- Promotion of nonalcoholic steatohepatitis by RNA NLife metabolism · 2022Article
- MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.Gastroenterology · 2022Article
- HepaticeLife · 2021Article
- Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledE2F transcription factor 1 (E2F1) is an important regulator of metabolic diseases; however, its role in liver function remains elusive. This study unraveled a regulatory cascade involving E2F1, early growth response-1 (Egr-1), nuclear receptor small heterodimer partner (SHP, NR0B2), and EIA-like inhibitor of differentiation 1 (EID1) in cholestatic liver fibrosis. Liver E2F1 messenger RNA (mRNA) and protein expression was strongly up-regulated in human nonalcoholic steatohepatitis (NASH) and alcohol cirrhosis; the latter was inversely correlated with diminished SHP expression. E2F1 was also highly induced by 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) feeding and bile-duct ligation (BDL) in mice. E2F1-/- mice exhibited reduced biliary fibrosis by DDC as determined by Masson Trichrome and Picro Sirius red staining, and decreased serum bile acid (BA), BA pool size, and fecal BA excretion. In addition, cholestatic liver fibrosis induced by BDL, as determined by immunohistochemistry analysis of a1 collagen expression, was increased in SHP-/- mice but attenuated in hepatocyte SHP-overexpressed transgenic (STG) mice. Egr-1 exhibited marked induction in livers of SHP-/- mice compared to the wild-type mice in both sham and BDL groups, and reduction in STG livers. Egr-1 promoter was activated by E2F1, and the activation was abrogated by expression of SHP and its co-repressor EID1 in hepatoma cells Huh7, Hepa1, and stellate cells LX2. Chromatin immunoprecipitation assays further confirmed the association of E2F1, SHP, and EID1 proteins with the Egr-1 promoter, and their direct protein interactions were determined by glutathione S-transferase pull-down assays. Interestingly, E2F1 activated Egr-1 expression in a biphasic fashion as described in both human and mouse hepatocytes.
conclusionE2F1 is a fibrogenic gene and could serve as a potential new diagnostic marker for nonalcoholic and alcoholic liver fibrosis/cirrhosis.
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