ArticleBMC pharmacology & toxicology2022
Overexpression of estrogen receptor β inhibits cellular functions of human hepatic stellate cells and promotes the anti-fibrosis effect of calycosin via inhibiting STAT3 phosphorylation.
Article in BMC pharmacology & toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 17 citations in OpenAlex.
- Comparing the Effect of Changes in Alcohol Intake on Liver Fibrosis Risk Scores Among Patients With Two Distinct Types of Steatotic Liver Disease.Journal of gastroenterology and hepatology · 2026Observational
- Cardiovascular Benefits of Menopause Hormone Treatment is Age-Dependent.bioRxiv : the preprint server for biology · 2026Article
- Calycosin protects from histopathological and ultrastructural changes in ethanol-induced liver injury and exhibits predicted binding affinity to TNF-α/NF-κB/HIF-1α proteins.Frontiers in pharmacology · 2026Article
- Idiopathic Pulmonary Fibrosis: Cellular Heterogeneity, Mechanisms, and Therapeutic Implications.MedComm · 2025Review
- Emerging Role of Calycosin in Inflammatory Diseases: Molecular Mechanisms and Potential Therapeutic Applications.Biomolecules · 2025Review
- Impact of aging and estrogen deficiency on extracellular matrix-related gene expression in rotator cuff tendons: in vitro and in vivo rat model.JSES international · 2025Article
- Sex-Dependent Regulation of Liver Fibrosis in Primary Sclerosing Cholangitis: The Role of miR-125b, Androgen Receptors, TGF-β, and Apelin Signalling.International journal of molecular sciences · 2025Article
- Sex differences in diet-induced MASLD - are female mice naturally protected?Frontiers in endocrinology · 2025Article
- The Influence of ESR2 Gene Polymorphisms on Susceptibility to Hepatitis B Virus-Related Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma.Biochemical genetics · 2024Article
- Genes Co-Expressed withInternational journal of molecular sciences · 2024Article
- Single-cell combined with transcriptome sequencing to explore the molecular mechanism of cell communication in idiopathic pulmonary fibrosis.Journal of cellular and molecular medicine · 2024Article
- Astragalus membranaceus and its monomers treat peritoneal fibrosis and related muscle atrophy through the AR/TGF-β1 pathway.Frontiers in pharmacology · 2024Article
- Mechanism and Progress of Natural Products in the Treatment of NAFLD-Related Fibrosis.Molecules (Basel, Switzerland) · 2023Review
- Sex differences in chronic liver disease and benign liver lesions.JHEP reports : innovation in hepatology · 2023Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEstrogen receptor β (ERβ) is the major ER subtype in hepatic stellate cells (HSCs). Previously we reported phytoestrogen calycosin suppressed liver fibrosis progression and inhibited HSC-T6 cell functions, suggesting the effects may be related to ERβ. Here, we explore the effect of overexpressed ERβ on human HSCs and the role of ERβ in pharmacological action of calycosin.
methodsLX-2 cells were transfected with lentivirus to overexpress ERβ. In the presence or absence of overexpressed ERβ, the effects of ERβ and calycosin on proliferation, migration, activation, collagen production and degradation of TGF-β1-induced LX-2 cells and the role of ERβ in the inhibition effect of calycosin were investigated. LX-2 cells overexpressed with ERβ or treated with ER non-selective antagonist ICI182,780 were used to investigate the regulation of ERβ on JAK2/STAT3 signaling pathway. CCK-8 method was used to screen effective doses of calycosin and investigate cell proliferation. The cell migration was detected by transwell chamber assay. The expression of α-SMA was detected by immunofluorescence and western blot. The protein expressions of Col-I, MMP1, TIMP1, JAK2, p-JAK2, STAT3 and p-STAT3 were detected by western blot.
resultsERβ overexpressed lentivirus was successfully transfected into LX-2 cells with high efficiency. Overexpressed ERβ or calycosin alone inhibited the TGF-β1-induced LX-2 cell proliferation and migration, downregulated the protein expressions of α-SMA, Col-I, TIMP-1, p-STAT3 and upregulated MMP-1. Both overexpressed ERβ and calycosin had no significant effect on JAK2, p-JAK2 and STAT3 expressions. ERβ overexpression further enhanced the above effects of calycosin. However, after the cells were treated with ICI182,780, downregulation of STAT3 phosphorylation induced by calycosin was reversed.
conclusionsERβ mediated the inhibition of major functions of LX-2 cell possibly by inhibiting the phosphorylation of STAT3, and was an important pathway through which calycosin exerted anti-liver fibrosis effect.
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