ArticleJCI insight2017
Synectin promotes fibrogenesis by regulating PDGFR isoforms through distinct mechanisms.
Article in JCI insight, 2017. 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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Who cites it
14 citing papers in PubMed.
- Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Angiocrine Signaling in Sinusoidal Health and Disease.Seminars in liver disease · 2023Review
- GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling.Oncology research · 2023Article
- Editorial: Chronic Liver Disease: New Targets and New Mechanisms, Volume II.Frontiers in molecular biosciences · 2023Article
- Human Hepatic Stellate Cells: Isolation and Characterization.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Role of extracellular vesicles in liver diseases and their therapeutic potential.Advanced drug delivery reviews · 2021Review
- Epigenetically Mediated Ciliogenesis and Cell Cycle Regulation, and Their Translational Potential.Cells · 2021Review
- Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12.Journal of hepatology · 2020Article
- GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway.Cellular and molecular gastroenterology and hepatology · 2020Article
- Transforming growth factor β (TGFβ) cross-talk with the unfolded protein response is critical for hepatic stellate cell activation.The Journal of biological chemistry · 2019Article
- Zeaxanthin Dipalmitate in the Treatment of Liver Disease.Evidence-based complementary and alternative medicine : eCAM · 2019Review
- Pericytes in the Liver.Advances in experimental medicine and biology · 2019Review
- Hepatic stellate cells - from past till present: morphology, human markers, human cell lines, behavior in normal and liver pathology.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologieReview
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
The scaffold protein synectin plays a critical role in the trafficking and regulation of membrane receptor pathways. As platelet-derived growth factor receptor (PDGFR) is essential for hepatic stellate cell (HSC) activation and liver fibrosis, we sought to determine the role of synectin on the PDGFR pathway and development of liver fibrosis. Mice with deletion of synectin from HSC were found to be protected from liver fibrosis. mRNA sequencing revealed that knockdown of synectin in HSC demonstrated reductions in the fibrosis pathway of genes, including PDGFR-β. Chromatin IP assay of the PDGFR-β promoter upon synectin knockdown revealed a pattern of histone marks associated with decreased transcription, dependent on p300 histone acetyltransferase. Synectin knockdown was found to downregulate PDGFR-α protein levels, as well, but through an alternative mechanism: protection from autophagic degradation. Site-directed mutagenesis revealed that ubiquitination of specific PDGFR-α lysine residues was responsible for its autophagic degradation. Furthermore, functional studies showed decreased PDGF-dependent migration and proliferation of HSC after synectin knockdown. Finally, human cirrhotic livers demonstrated increased synectin protein levels. This work provides insight into differential transcriptional and posttranslational mechanisms of synectin regulation of PDGFRs, which are critical to fibrogenesis.
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Registered trials
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