ArticleCell death & disease2017
The functional relationship between transglutaminase 2 and transforming growth factor β1 in the regulation of angiogenesis and endothelial-mesenchymal transition.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Transglutaminase 2 modulates inflammatory angiogenesis via vascular endothelial growth factor receptor 2 pathway in inflammatory bowel disease.Journal of advanced research · 2026Article
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- A comprehensive approach to elucidating the pathophysiology of kidney fibrosis based on extracellular vesicle proteomics.Frontiers in physiology · 2026Article
- Targeting the Primordial Chaperone to Overcome Acquired Drug Resistance in Cancer: TG2-Mediated Autophagy.Biomolecules & therapeutics · 2026Review
- Loss of fibronectin fiber tension is inherent to ECM remodeling in human myocarditis and post-inflammatory fibrosis.Matrix biology plus · 2025Article
- FDA-approved drug repurposing in zebrafish identifies thyroid hormone and other compounds as potential antithrombotics.bioRxiv : the preprint server for biology · 2025Article
- Role of the TGF‑β/Smad signaling pathway in the transition from acute kidney injury to chronic kidney disease (Review).International journal of molecular medicine · 2025Review
- Transglutaminase 2 in human peritoneal dialysis-related peritoneal injury.Physiological reports · 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
- Biochemical and Functional Characterization of the Three Zebrafish Transglutaminases 2.International journal of molecular sciences · 2023Article
- Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid.Cell death & disease · 2023Article
- Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis.Biomedicines · 2022Article
- Review
- Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts.International journal of molecular sciences · 2021Article
- Vocal Fold Fibroblasts in Reinke's Edema Show Alterations Involved in Extracellular Matrix Production, Cytokine Response and Cell Cycle Control.Biomedicines · 2021Article
- Transglutaminase 2: a novel therapeutic target for idiopathic pulmonary fibrosis using selective small molecule inhibitors.Amino acids · 2021Article
- Inhibition of TGF-β2-induced migration and epithelial-mesenchymal transition in ARPE-19 by sulforaphane.International journal of ophthalmology · 2021Article
- Platelet-Released Growth Factors and Platelet-Rich Fibrin Induce Expression of Factors Involved in Extracellular Matrix Organization in Human KeratinocytesInternational journal of molecular sciences · 2020Article
- Moonlighting Proteins Are Important Players in Cancer Immunology.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The importance of transglutaminase 2 (TG2) in angiogenesis has been highlighted in recent studies, but other roles of this multi-functional enzyme in endothelial cell (EC) function still remains to be fully elucidated. We previously showed that the extracellular TG2 is involved in maintaining tubule formation in ECs by a mechanism involving matrix-bound vascular endothelial growth factor (VEGF) signalling. Here, by using the ECs and fibroblast co-culture and ECs 3D culture models, we demonstrate a further role for TG2 in both endothelial tubule formation and in tubule loss, which involves its role in the regulation of transforming growth factor β1 (TGFβ1) and Smad signalling. We demonstrate that inhibition of tubule formation by TG2 inhibitors can be restored by add-back of exogenous TGFβ1 at pg/ml levels and show that TG2 -/- mouse ECs are unable to form tubules in 3D culture and display negligible Smad signalling compared to wild-type cells. Loss of tubule formation in the TG2 -/- ECs can be reconstituted by transduction with TG2. We demonstrate that extracellular TG2 also has an important role in TGFβ1-induced transition of ECs into myofibroblast-like cells (endothelial-mesenchymal transition), resulting in loss of EC tubules and tubule formation. Our data also indicate that TG2 may have a role in regulating TGFβ signalling through entrapment of active TGFβ1 into the extracellular matrix. In conclusion, our work demonstrates that TG2 has multi-functional roles in ECs where its ability to fine-tune of TGFβ1 signalling means it can be involved in both endothelial tubule formation and tubule rarefaction.
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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.