ArticleBlood2021
Factor XIII cross-links fibrin(ogen) independent of fibrin polymerization in experimental acute liver injury.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Factor XIII Deficiency: A Review of Biology, Testing, and Treatment.Clinical hematology international · 2026Review
- Fibrinogen in extracellular matrix remodeling: functional switching, source heterogeneity, and biomaterial translation.Frontiers in cell and developmental biology · 2026Review
- Integrated cross-linking by TG2 and FXIII generates hepatoprotective fibrin(ogen) deposits in injured liver.Blood · 2025Article
- Activation of the Coagulation Cascade as a Universal Danger Sign.Current issues in molecular biology · 2025Review
- Determinants of abnormal liver-related biomarkers in adult COVID-19 patients.Frontiers in cellular and infection microbiology · 2025Article
- Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots.International journal of molecular sciences · 2024Article
- Fibrinolysis-Mediated Pathways in Acute Liver Injury.Seminars in thrombosis and hemostasis · 2024Review
- Intraoperative bioprinting of human adipose-derived stem cells and extra-cellular matrix induces hair follicle-like downgrowths and adipose tissue formation during full-thickness craniomaxillofacial skin reconstruction.Bioactive materials · 2024Article
- Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression.Molecular oncology · 2024Article
- Neutrophil-dependent hepatic platelet accumulation and liver injury revealed by acetaminophen dose-response studies.Research and practice in thrombosis and haemostasis · 2024Article
- Fungi Fibrinolytic Compound 1 Plays a Core Role in Modulating Fibrinolysis, Altering Plasma Clot Structure, and Promoting Susceptibility to Lysis.Pharmaceutics · 2023Article
- Robust coagulation activation and coagulopathy in mice with experimental acetaminophen-induced liver failure.Journal of thrombosis and haemostasis : JTH · 2023Article
- Altered fibrinogen γ-chain cross-linking in mutant fibrinogen-γJournal of thrombosis and haemostasis : JTH · 2023Article
- Thrombus composition and thrombolysis resistance in stroke.Research and practice in thrombosis and haemostasis · 2023Article
- Fibrin clot properties and thrombus composition in cirrhosis.Research and practice in thrombosis and haemostasis · 2023Article
- Elimination of fibrin polymer formation or crosslinking, but not fibrinogen deficiency, is protective against diet-induced obesity and associated pathologies.Journal of thrombosis and haemostasis : JTH · 2022Article
- SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19.International journal of laboratory hematology · 2022Article
- Cross-linking by tissue transglutaminase-2 alters fibrinogen-directed macrophage proinflammatory activity.Journal of thrombosis and haemostasis : JTH · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Intravascular fibrin clot formation follows a well-ordered series of reactions catalyzed by thrombin cleavage of fibrinogen leading to fibrin polymerization and cross-linking by factor XIIIa (FXIIIa). Extravascular fibrin(ogen) deposits are observed in injured tissues; however, the mechanisms regulating fibrin(ogen) polymerization and cross-linking in this setting are unclear. The objective of this study was to determine the mechanisms of fibrin polymerization and cross-linking in acute liver injury induced by acetaminophen (APAP) overdose. Hepatic fibrin(ogen) deposition and cross-linking were measured following APAP overdose in wild-type mice, mice lacking the catalytic subunit of FXIII (FXIII-/-), and in FibAEK mice, which express mutant fibrinogen insensitive to thrombin-mediated fibrin polymer formation. Hepatic fibrin(ogen) deposition was similar in APAP-challenged wild-type and FXIII-/- mice, yet cross-linking of hepatic fibrin(ogen) was dramatically reduced (>90%) by FXIII deficiency. Surprisingly, hepatic fibrin(ogen) deposition and cross-linking were only modestly reduced in APAP-challenged FibAEK mice, suggesting that in the APAP-injured liver fibrin polymerization is not strictly required for the extravascular deposition of cross-linked fibrin(ogen). We hypothesized that the oxidative environment in the injured liver, containing high levels of reactive mediators (eg, peroxynitrite), modifies fibrin(ogen) such that fibrin polymerization is impaired without impacting FXIII-mediated cross-linking. Notably, fibrin(ogen) modified with 3-nitrotyrosine adducts was identified in the APAP-injured liver. In biochemical assays, peroxynitrite inhibited thrombin-mediated fibrin polymerization in a concentration-dependent manner without affecting fibrin(ogen) cross-linking over time. These studies depict a unique pathology wherein thrombin-catalyzed fibrin polymerization is circumvented to allow tissue deposition and FXIII-dependent fibrin(ogen) cross-linking.
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Registered trials
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 OpenQuestion graph.