ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Nrf2 Ameliorates DDC-Induced Sclerosing Cholangitis and Biliary Fibrosis and Improves the Regenerative Capacity of the Liver.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 29 citations in OpenAlex.
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- Fibroblast Upregulation of Vitamin D Receptor Represents a Self-Protective Response to Limit Fibroblast Proliferation and Activation during Pulmonary Fibrosis.Antioxidants (Basel, Switzerland) · 2023Article
- The Contribution of the Nrf2/ARE System to Mechanotransduction in Musculoskeletal and Periodontal Tissues.International journal of molecular sciences · 2023Review
- Nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency causes age-dependent progression of female osteoporosis.BMC musculoskeletal disorders · 2022Article
- Nrf2 induces malignant transformation of hepatic progenitor cells by inducing β-catenin expression.Redox biology · 2022Article
- Physiological Mineralization during In Vitro Osteogenesis in a Biomimetic Spheroid Culture Model.Cells · 2022Article
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- Nrf2/ARE Signaling Directly Regulates SOX9 to Potentially Alter Age-Dependent Cartilage Degeneration.Antioxidants (Basel, Switzerland) · 2022Article
- Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis.Open medicine (Warsaw, Poland) · 2022Review
- The Nrf2 Pathway in Liver Diseases.Frontiers in cell and developmental biology · 2022Review
- Sulforaphane Exerts Beneficial Immunomodulatory Effects on Liver TissueFrontiers in immunology · 2022Article
- Biliary Epithelial Senescence in Liver Disease: There Will Be SASP.Frontiers in molecular biosciences · 2021Review
- Cell Sources and Influencing Factors of Liver Regeneration: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2020Review
- Nrf2 in liver toxicology.Archives of pharmacal research · 2020Review
- Yellow Wine Polyphenolic Compounds prevents Doxorubicin-induced cardiotoxicity through activation of the Nrf2 signalling pathway.Journal of cellular and molecular medicine · 2019Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The Nrf2 pathway protects against oxidative stress and induces regeneration of various tissues. Here, we investigated whether Nrf2 protects from sclerosing cholangitis and biliary fibrosis and simultaneously induces liver regeneration. Diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was fed to Nrf2-KO mice (Nrf2-/-), mice with liver-specific hyperactivated Nrf2 (HKeap1-/-) and wild-type (WT) littermates to induce cholangitis, liver fibrosis, and oval cell expansion. HKeap1-/--mice were protected from almost all DDC-induced injury compared with WT and Nrf2-/-. Liver injury in Nrf2-/- and WT mice was mostly similar, albeit Nrf2-/- suffered more from DDC diet as seen for several parameters. Nrf2 activity was especially important for the expression of the hepatic efflux transporters Abcg2 and Abcc2-4, which are involved in hepatic toxin elimination. Surprisingly, cell proliferation was more enhanced in Nrf2-/-- and HKeap1-/--mice compared with WT. Interestingly, Nrf2-/--mice failed to sufficiently activate oval cell expansion after DDC treatment and showed almost no resident oval cell population under control conditions. The resident oval cell population of untreated HKeap1-/--mice was increased and DDC treatment resulted in a stronger oval cell expansion compared with WT. We provide evidence that Nrf2 activation protects from DDC-induced sclerosing cholangitis and biliary fibrosis. Moreover, our data establish a possible role of Nrf2 in oval cell expansion.
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