Evidence map›Paper›PMID 35158413›Full record

ArticleJournal of thrombosis and haemostasis : JTH2022

Cross-linking by tissue transglutaminase-2 alters fibrinogen-directed macrophage proinflammatory activity.

Lauren G Poole, Anna K Kopec, Matthew J Flick, James P Luyendyk

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Red blood cell-derived transglutaminase 2 influences thrombus formation.Research and practice in thrombosis and haemostasis · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Targeted intervention in obesity-associated atrial fibrosis using nanoparticle-loaded fusion protein.Apoptosis : an international journal on programmed cell death · 2025
    Article
  9. Article
  10. Deconstructing fibrin(ogen) structure.Journal of thrombosis and haemostasis : JTH · 2025
    Review
  11. Article
  12. Article
  13. Fibrinogen and tumors.Frontiers in oncology · 2024
    Review
  14. Article
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Lauren G PooleDepartment of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA.ORCID 0000-0002-5405-5774
Anna K KopecDepartment of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA.
Matthew J FlickDepartment of Pathology and Laboratory Medicine, UNC Blood Research Center, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
James P LuyendykDepartment of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA.ORCID 0000-0003-3174-8583
Michigan State University · USUniversity of North Carolina at Chapel Hill · US

Funding

Novel anti-fibrotic mechanisms in chemical-induced liver injuryR01ES017537 · NIEHS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI LUYENDYK, JAMES P · 2009 to 2019
$3.6M
Novel determinants of fibrinogen pro-repair activity in acetaminophen-induced liver toxicityR01DK120289 · NIDDK · MICHIGAN STATE UNIVERSITY · PI LUYENDYK, JAMES P · 2019 to 2023
$2.2M
Fibrin(ogen) control of metabolic inflammation and obesityR01DK112778 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FLICK, MATTHEW J. · 2019 to 2022
$1.5M
Novel mechanisms linking blood coagulation to liver fibrosisK99DK129710 · NIDDK · MICHIGAN STATE UNIVERSITY · PI POOLE, LAUREN G · 2021 to 2022
$177k
Mechanisms of fibrin(ogen)-directed macrophage activation in liver toxicityF32DK121423 · NIDDK · MICHIGAN STATE UNIVERSITY · PI POOLE, LAUREN G · 2019 to 2019
$62k
NIDDK NIH HHS F32 DK121423NIDDK NIH HHS K99 DK129710NIDDK NIH HHS R01 DK112778NIDDK NIH HHS R01 DK120289NIEHS NIH HHS R01 ES017537
6 · The paper itself

Abstract

backgroundThe blood coagulation factor fibrin(ogen) can modulate inflammation by altering leukocyte activity. Analyses of fibrin(ogen)-mediated proinflammatory activity have largely focused on leukocyte integrin binding activity revealed by conversion of fibrinogen to a stabilized fibrin polymer by blood coagulation enzymes. In addition to coagulation enzymes, fibrinogen is a substrate for tissue transglutaminase-2 (TG2), a widely expressed enzyme that produces unique fibrinogen Aα-γ chain cross-linked products.

objectivesWe tested the hypothesis that TG2 dependent cross-linking alters the proinflammatory activity of surface-adhered fibrinogen.

methodsMouse bone marrow-derived macrophages (BMDMs) were cultured on tissue culture plates coated with fibrinogen or TG2-cross-linked fibrinogen (10 µg/ml) and then stimulated with lipopolysaccharide (LPS, 1 ng/ml) or vehicle for various times.

resultsIn the absence of LPS stimulation, TG2-cross-linked fibrin(ogen) enhanced inflammatory gene induction (e.g., Tnfα) compared with unmodified fibrinogen. LPS stimulation induced mitogen-activated protein kinase phosphorylation, IκBα degradation, and expression of proinflammatory cytokines (e.g., tumor necrosis factor α) within 60 min. This initial cellular activation was unaffected by unmodified or TG2-cross-linked fibrinogen. In contrast, LPS induction of interleukin-10 mRNA and protein and STAT3 phosphorylation was selectively attenuated by TG2-cross-linked fibrinogen, which was associated with enhanced proinflammatory cytokine secretion by LPS-stimulated BMDMs at later time points (6 and 24 h).

conclusionsThe results indicate that atypical cross-linking by TG2 imparts unique proinflammatory activity to surface-adhered fibrinogen. The results suggest a novel coagulation-independent mechanism controlling fibrinogen-directed macrophage activation.

Indexed as

LipopolysaccharidesProtein Glutamine gamma Glutamyltransferase 2AnimalsFibrinFibrinogenHumansMacrophagesMiceTransglutaminasesTumor Necrosis Factor-alphaFibrinFibrinogenLipopolysaccharidesProtein Glutamine gamma Glutamyltransferase 2Tgm2 protein, mouseTransglutaminasesTumor Necrosis Factor-alphafibrinogeninflammationlipopolysaccharidemacrophagetransglutaminase

Identifiers

PMID35158413
PMCPMC9035112
OpenAlexW4213019009

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.