ArticleCellular and molecular gastroenterology and hepatology2020
GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- [Novel advances following the integration of Baveno VII consensus definitions for the non-invasive testing of portal hypertension].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Single cell multiomic landscape reveals gene programs driving lipid droplet heterogeneity in hepatic steatosis.Scientific reports · 2026Article
- Knockout of IGFBP3 improves alcohol-induced liver injury via Akt/GSK3β and TMEM219/caspase 8 pathways.Frontiers in physiology · 2026Article
- Insulin-like growth factor binding proteins in metabolic dysfunction-associated steatotic liver disease.Frontiers in endocrinology · 2026Review
- A Functional Shift of IGFBP3 in Osteoarthritis: From Cartilage Protection to Disease Promotion.Journal of inflammation research · 2026Review
- Pathologic Signaling and Disease Implications of Insulin-like Growth Factor Binding Proteins in Cancer, Cardiovascular Disease, and Fibrosis.International journal of molecular sciences · 2025Review
- IGFBP3 modulation of tumor pathogenesis and cell signaling pathways (Review).Oncology letters · 2025Review
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front.Cancer gene therapy · 2024Article
- Insulin-like Growth Factor Binding Proteins and Cellular Senescence Are Involved in the Progression of Non-Alcoholic Fatty Liver Disease and Fibrosis in a Mouse Model.Medicina (Kaunas, Lithuania) · 2024Article
- Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead.Acta pharmaceutica Sinica. B · 2024Review
- Signaling Pathways of the Insulin-like Growth Factor Binding Proteins.Endocrine reviews · 2023Article
- Angiocrine Signaling in Sinusoidal Health and Disease.Seminars in liver disease · 2023Review
- Editorial: Chronic Liver Disease: New Targets and New Mechanisms, Volume II.Frontiers in molecular biosciences · 2023Article
- Article
- Induced Pluripotent Stem Cells From Subjects With Primary Sclerosing Cholangitis Develop a Senescence Phenotype Following Biliary Differentiation.Hepatology communications · 2022Article
- Ferulic Acid Combined With Bone Marrow Mesenchymal Stem Cells Attenuates the Activation of Hepatic Stellate Cells and Alleviates Liver Fibrosis.Frontiers in pharmacology · 2022Article
- Development of human iPSC-derived quiescent hepatic stellate cell-like cells for drug discovery and in vitro disease modeling.Stem cell reports · 2021Article
- Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C-C Motif Chemokine Ligand 2-Mediated Angiocrine Signaling.Hepatology (Baltimore, Md.) · 2021Article
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Authors and funding
14 authors at 1 institution in 4 countries.
Funding
Abstract
BACKGROUND &
aimsTransforming growth factor (TGF-β)-induced activation of quiescent hepatic stellate cells (HSCs) and their transformation to myofibroblasts is a key event in liver fibrosis and portal hypertension. GIPC (also referred to as synectin) is a downstream signal activation molecule of TGF-β and other receptors. In this study, we sought to identify novel genes targeted by TGF-β and GIPC and elucidate if and how they may contribute to liver fibrosis.
methodsWe performed sequential messenger RNA sequencing analysis on TGF-β-stimulated HSCs and then on TGF-β-stimulated HSCs in the presence and absence of GIPC also referred to as synectin (GIPC) knockdown. Insulin-like growth factor binding protein-3 (IGFBP-3) transport protein emerged as a top activation target of both TGF-β and GIPC. Quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, targeted chromatin immunoprecipitation, and Western blot analysis were done for further confirmation.
resultsIGFBP-3, an insulin growth factor transport protein, emerged as a top activation target of both TGF-β and GIPC, which was confirmed by quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot analysis. Targeted chromatin immunoprecipitation showed that GIPC increases the histone 3 lysine 27 (H3K27) acetylation activating mark and concurrently decreases the H3K27 inhibitory trimethylation (H3K27m3) mark, providing an epigenetic correlate to the gene regulation changes. In vivo, global knockout of IGFBP-3 mice resulted in attenuation of HSC activation markers and attenuation of portal pressure in response to chronic liver injury models. Analysis of serum levels from cirrhotic patients also showed an IGFBP-3 increase of more than 2-fold compared with healthy controls. Finally, in vitro mechanism studies showed that IGFBP-3 promotes HSC migration through integrin-dependent phosphorylation of protein kinase B.
conclusionsTGF-β up-regulates IGFBP-3 through GIPC, leading to increased HSC migration in vitro and promotes portal hypertension in vivo. These studies support the role of IGFBP-3 as a potential pathophysiologic target or biomarker in chronic liver disease.
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