ArticleJournal of thrombosis and haemostasis : JTH2023
Novel genetic regulators of fibrinogen synthesis identified by an in vitro experimental platform.
Article in Journal of thrombosis and haemostasis : JTH, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- Inflammation-coagulation biomarkers predict catheter-related thrombosis following peripherally inserted central catheter placement in patients with hematologic malignancies: a retrospective cohort study.Translational cancer research · 2026Article
- Hepatic Mechanisms and Therapeutic Target Underpinning Hypercoagulation in Obesity: Insights From Genetic and Transcriptomic Analyses.Exploration (Beijing, China) · 2026Article
- Historical review: more than two decades understanding the genetic architecture of hemostasis and thrombosis.Journal of thrombosis and haemostasis : JTH · 2026Review
- Hepatic targeting in ASCVD: integrating lipid lowering and inflammation modulation from statins to gene editing.Journal of translational medicine · 2026Review
- Predictive Value of the FDAPR Index for Ischemic Stroke in Patients with Coronary Heart Disease: A Machine Learning Study Based on a Multilayer Perceptron.International journal of general medicine · 2026Article
- Genetic pleiotropy underlying obesity and autoimmune disorders: a large-scale cross-trait gwas analysis in European ancestry populations.Journal of translational medicine · 2025Article
- The Interconnected World of Coagulation Factors, Platelets and Plasminogen: A Novel Perspective on Biosynthetic Regulation.Life (Basel, Switzerland) · 2025Review
- Development and validation of a risk prediction model for venous thromboembolism after surgery in elderly patients with lung cancer.BMC surgery · 2025Article
- Venous Thromboembolic Events in Cancer Immunotherapy: A Narrative Review.Journal of clinical medicine · 2025Review
- Regulation of fibrinogen synthesis.Thrombosis research · 2024Review
- The emerging role of fibrin(ogen) in cardiovascular disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Fibrinogen and fibrin: synthesis, structure, and function in health and disease.Journal of thrombosis and haemostasis : JTH · 2023Review
- Standardization of Animal Models and Techniques for Platelet-Rich Fibrin Production: A Narrative Review and Guideline.Bioengineering (Basel, Switzerland) · 2023Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundFibrinogen has an established, essential role in both coagulation and inflammatory pathways, and these processes are deeply intertwined in the development of thrombotic and atherosclerotic diseases. Previous studies aimed to better understand the (patho) physiological actions of fibrinogen by characterizing the genomic contribution to circulating fibrinogen levels.
objectivesEstablish an in vitro approach to define functional roles between genes within these loci and fibrinogen synthesis.
methodsCandidate genes were selected on the basis of their proximity to genetic variants associated with fibrinogen levels and expression in hepatocytes and HepG2 cells. HepG2 cells were transfected with small interfering RNAs targeting candidate genes and cultured in the absence or presence of the proinflammatory cytokine interleukin-6. Effects on fibrinogen protein production, gene expression, and cell growth were assessed by immunoblotting, real-time polymerase chain reaction, and cell counts, respectively.
resultsHepG2 cells secreted fibrinogen, and stimulation with interleukin-6 increased fibrinogen production by 3.4 ± 1.2 fold. In the absence of interleukin-6, small interfering RNA knockdown of FGA, IL6R, or EEPD1 decreased fibrinogen production, and knockdown of LEPR, PDIA5, PLEC, SHANK3, or CPS1 increased production. In the presence of interleukin-6, knockdown of FGA, IL6R, or ATXN2L decreased fibrinogen production. Knockdown of FGA, IL6R, EEPD1, LEPR, PDIA5, PLEC, or CPS1 altered transcription of one or more fibrinogen genes. Knocking down ATXN2L suppressed inducible but not basal fibrinogen production via a post-transcriptional mechanism.
conclusionsWe established an in vitro platform to define the impact of select gene products on fibrinogen production. Genes identified in our screen may reveal cellular mechanisms that drive fibrinogen production as well as fibrin(ogen)-mediated (patho)physiological mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.