ArticlePloS one2010
E3 ubiquitin ligase synoviolin is involved in liver fibrogenesis.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 92 citations in OpenAlex.
- E3 Ubiquitin Ligases in MASH-Associated Liver Fibrosis: Mechanisms and Therapeutic Opportunities.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- MYC affects mitochondrial function in IgA nephropathy by promoting the degradation of MFN1 through HRD1.Immunologic research · 2025Article
- Arctigenin Attenuates Hepatic Stellate Cell Activation via Endoplasmic Reticulum-Associated Degradation (ERAD)-Mediated Restoration of Lipid Homeostasis.Journal of agricultural and food chemistry · 2025Article
- Nedd4L signaling contributes to carbon tetrachloride-induced liver fibrosis in female mice and is associated with enteric dysbacteriosis.Gastroenterology report · 2025Article
- Synoviolin alleviates GSDMD-mediated periodontitis by suppressing its stability.Immunity, inflammation and disease · 2023Article
- Structural changes of proteins in liver cirrhosis and consequential changes in their function.World journal of gastroenterology · 2022Review
- E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis.Cell death & disease · 2022Article
- Multi-Omics Integration Highlights the Role of Ubiquitination in CClInternational journal of molecular sciences · 2020Article
- Induction of E6AP by microRNA-302c dysregulation inhibits TGF-β-dependent fibrogenesis in hepatic stellate cells.Scientific reports · 2020Article
- Review
- Astaxanthin ameliorates renal interstitial fibrosis and peritubular capillary rarefaction in unilateral ureteral obstruction.Molecular medicine reports · 2019Article
- Ubiquitination and deubiquitination emerge as players in idiopathic pulmonary fibrosis pathogenesis and treatment.JCI insight · 2018Review
- Ubiquitination in Scleroderma Fibrosis and Its Treatment.Frontiers in immunology · 2018Review
- Hrd1 and ER-Associated Protein Degradation, ERAD, are Critical Elements of the Adaptive ER Stress Response in Cardiac Myocytes.Circulation research · 2015Article
- The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β.The EMBO journal · 2015Article
- Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis.Genes & development · 2014Article
- Hrd1 participates in the regulation of collagen I synthesis in renal fibrosis.Molecular and cellular biochemistry · 2014Article
- Protein quality control in the endoplasmic reticulum.F1000prime reports · 2014Review
- Article
- RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis.International journal of molecular medicine · 2012Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimChronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis.
methodsThe expression and localization of synoviolin in the liver were analyzed in CCl(4)-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno(+/-) mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno(+/-) mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno(-/-) mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno(-/-) MEF cells.
resultsIn the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno(+/-) mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno(+/-) mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno(-/-) MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum.
conclusionOur findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis.
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