ArticleCell death & disease2018
Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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.
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Who cites it
51 citing papers in PubMed, 92 citations in OpenAlex.
- Randomized Phase 1 Studies Evaluating the Safety, Tolerability, Pharmacokinetics, and Target Occupancy of Zampilimab in Healthy Participants.Clinical pharmacology in drug development · 2026Trial
- Trial
- Endothelial PARP1 orchestrates endothelial-to-mesenchymal transition via the PARylation of FHL2 in ischaemic heart failure.Acta pharmacologica Sinica · 2026Article
- Cardiac fibrosis: mechanistic insights and translational advances.Molecular biomedicine · 2026Review
- Heart-derived factors and organ cross-talk in settings of health and disease: new knowledge and clinical opportunities for multimorbidity.The Journal of physiology · 2026Review
- SPECT as a translational non-invasive method to assess occupancy of the tissue transglutaminase-2 by zampilimab in the mouse lung.Respiratory research · 2026Article
- Collagen in Fibrotic Diseases.Sub-cellular biochemistry · 2026Review
- Loss of fibronectin fiber tension is inherent to ECM remodeling in human myocarditis and post-inflammatory fibrosis.Matrix biology plus · 2025Article
- Critical Role for Transglutaminase 2 in Scleroderma Skin Fibrosis and in the Development of Dermal Sclerosis in a Mouse Model of Scleroderma.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Article
- Transglutaminase 2 knockout mice are protected from bleomycin-induced lung fibrosis with preserved lung function and reduced metabolic derangements.Physiological reports · 2024Article
- Review
- Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Transglutaminase 2 inhibition ameliorates cardiac fibrosis in myocardial infarction by inducing M2 macrophage polarizationCytoJournal · 2024Article
- Article
- SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1.Cardiovascular diabetology · 2023Article
- Insulin-Like Growth Factor 1 Receptor Deficiency Alleviates Angiotensin II-Induced Cardiac Fibrosis Through the Protein Kinase B/Extracellular Signal-Regulated Kinase/Nuclear Factor-κB Pathway.Journal of the American Heart Association · 2023Article
- Mitigation of Fibrosis after Myocardial Infarction in Rats by Using a Porcine Cholecyst Extracellular Matrix.Comparative medicine · 2023Article
- Review
- How the mechanobiology orchestrates the iterative and reciprocal ECM-cell cross-talk that drives microtissue growth.Science advances · 2023Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Cardiac fibrosis is implicit in all forms of heart disease but there are no effective treatments. In this report, we investigate the role of the multi-functional enzyme Transglutaminase 2 (TG2) in cardiac fibrosis and assess its potential as a therapeutic target. Here we describe the use a highly selective TG2 small-molecule inhibitor to test the efficacy of TG2 inhibition as an anti-fibrotic therapy for heart failure employing two different in vivo models of cardiac fibrosis: Progressively induced interstitial cardiac fibrosis by pressure overload using angiotensin II infusion: Acutely induced focal cardiac fibrosis through myocardial infarction by ligation of the left anterior descending coronary artery (AMI model). In the AMI model, in vivo MRI showed that the TG2 inhibitor 1-155 significantly reduced infarct size by over 50% and reduced post-infarct remodelling at 20 days post insult. In both models, Sirius red staining for collagen deposition and levels of the TG2-mediated protein crosslink ε(γ-glutamyl)lysine were significantly reduced. No cardiac rupture or obvious signs of toxicity were observed. To provide a molecular mechanism for TG2 involvement in cardiac fibrosis, we show that both TGFβ1-induced transition of cardiofibroblasts into myofibroblast-like cells and TGFβ1-induced EndMT, together with matrix deposition, can be attenuated by the TG2 selective inhibitor 1-155, suggesting a new role for TG2 in regulating TGFβ1 signalling in addition to its role in latent TGFβ1 activation. In conclusion, TG2 has a role in cardiac fibrosis through activation of myofibroblasts and matrix deposition. TG2 inhibition using a selective small-molecule inhibitor can attenuate cardiac fibrosis.
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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.