Tissue transglutaminase in fibrosis — more than an extracellular matrix cross-linker

Benn, Mario C.; Weber, Willi; Klotzsch, Enrico; Vogel, Viola; Pot, Simon A.

doi:10.1016/j.cobme.2019.06.003

Cited by 31 publications

(41 citation statements)

References 74 publications

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“…In RA patients and in the CIA mice model, the synovial membrane or synovial fluid shows increased levels of EMT-inducing molecules, including TGF-β [ 150 ]. Some highly innovative studies reported that TGF-β was up-regulated by transglutaminase 2 (TG2), an important enzyme in the regulation of EMT and ECM composition/stiffness/degradation [ 151 ]. TG2 was shown to play a key role in invadosome formation by fibroblast-like synoviocytes (RA-FLS), through its ability to cross-link with the ECM and to determine the activation of TGF-β [ 152 ].…”

Section: Tgf-β-induced Emt: Molecular Mechanisms In Rheumatoid Artmentioning

confidence: 99%

Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

2021

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Recent advances in our understanding of the molecular pathways that control the link of inflammation with organ fibrosis and autoimmune diseases point to the epithelial to mesenchymal transition (EMT) as the common association in the progression of these diseases characterized by an intense inflammatory response. EMT, a process in which epithelial cells are gradually transformed to mesenchymal cells, is a major contributor to the pathogenesis of fibrosis. Importantly, the chronic inflammatory microenvironment has emerged as a decisive factor in the induction of pathological EMT. Transforming growth factor-β (TGF-β), a multifunctional cytokine, plays a crucial role in the induction of fibrosis, often associated with chronic phases of inflammatory diseases, contributing to marked fibrotic changes that severely impair normal tissue architecture and function. The understanding of molecular mechanisms underlying EMT-dependent fibrosis has both a basic and a translational relevance, since it may be useful to design therapies aimed at counteracting organ deterioration and failure. To this end, we reviewed the recent literature to better elucidate the molecular response to inflammatory/fibrogenic signals in autoimmune diseases in order to further the specific regulation of EMT-dependent fibrosis in more targeted therapies.

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Section: Tgf-β-induced Emt: Molecular Mechanisms In Rheumatoid Artmentioning

confidence: 99%

Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

2021

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“…The relation between syndecan-4 and TG2 on the surface of macrophages is significant, as it seems to support the recruitment and migration against apoptotic or unfunctional cells, ultimately protecting from a chronic inflammatory state [ 142 ]; and extracellular release performed through syndecan-4 promotes TG2 to contribute to cross-linking of the ECM, which is a contributor to fibrosis [ 143 ]. The ECM of the TME bears a lot of the hallmarks of a fibrotic response, with dense collagen deposition and cross-linking [ 144 , 145 ]. The link between TAMs, ECM remodelling in cancer [ 146 ], and TG2 is currently under-explored, and given the growing evidence that TAM/CAF-mediated remodelling appears critical to the exclusion of anti-cancer immune responses [ 147 ], further work in this field would be informative.…”

Section: Tg2 As a Key Functional Player In The Tmementioning

confidence: 99%

The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment

Tempest

Guarnerio

Maani

et al. 2021

Cancers

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Transglutaminase-2 (TG2) is the most highly and ubiquitously expressed member of the transglutaminase enzyme family and is primarily involved in protein cross-linking. TG2 has been implicated in the development and progression of numerous cancers, with a direct role in multiple cellular processes and pathways linked to apoptosis, chemoresistance, epithelial-mesenchymal transition, and stem cell phenotype. The tumour microenvironment (TME) is critical in the formation, progression, and eventual metastasis of cancer, and increasing evidence points to a role for TG2 in matrix remodelling, modulation of biomechanical properties, cell adhesion, motility, and invasion. There is growing interest in targeting the TME therapeutically in response to advances in the understanding of its critical role in disease progression, and a number of approaches targeting biophysical properties and biomechanical signalling are beginning to show clinical promise. In this review we aim to highlight the wide array of processes in which TG2 influences the TME, focussing on its potential role in the dynamic tissue remodelling and biomechanical events increasingly linked to invasive and aggressive behaviour. Drug development efforts have yielded a range of TG2 inhibitors, and ongoing clinical trials may inform strategies for targeting the biomolecular and biomechanical function of TG2 in the TME.

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“…23 In addition, it has an important function in mediating cell−matrix interactions. 24 Moreover, apart from neoplastic malignancies, the enzyme is involved in the pathogenesis of several other diseases, 25 of which celiac disease is the most prominent example. 26,27 TGase 2 represents a multifunctional protein that is composed of four domains.…”

Section: ■ Introductionmentioning

confidence: 99%

Development of an ¹⁸F-Labeled Irreversible Inhibitor of Transglutaminase 2 as Radiometric Tool for Quantitative Expression Profiling in Cells and Tissues

Wodtke

Hauser

et al. 2021

J. Med. Chem.

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The transamidase activity of transglutaminase 2 (TGase 2) is considered to be important for several pathophysiological processes including fibrotic and neoplastic tissue growth, whereas in healthy cells this enzymatic function is predominantly latent. Methods that enable the highly sensitive detection of TGase 2, such as application of radiolabeled activity-based probes, will support the exploration of the enzyme’s function in various diseases. In this context, the radiosynthesis and detailed in vitro radiopharmacological evaluation of an 18F-labeled N ε-acryloyllysine piperazide are reported. Robust and facile detection of the radiotracer-TGase 2 complex by autoradiography of thin layer plates and polyacrylamide gels after chromatographic and electrophoretic separation owing to irreversible covalent bond formation was demonstrated for the isolated protein, cell lysates, and living cells. By use of this radiotracer, quantitative data on the expression profile of activatable TGase 2 in mouse organs and selected tumors were obtained for the first time by autoradiography of tissue sections.

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Tissue transglutaminase in fibrosis — more than an extracellular matrix cross-linker

Cited by 31 publications

References 74 publications

Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment

Development of an ¹⁸F-Labeled Irreversible Inhibitor of Transglutaminase 2 as Radiometric Tool for Quantitative Expression Profiling in Cells and Tissues

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Tissue transglutaminase in fibrosis — more than an extracellular matrix cross-linker

Cited by 31 publications

References 74 publications

Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment

Development of an 18F-Labeled Irreversible Inhibitor of Transglutaminase 2 as Radiometric Tool for Quantitative Expression Profiling in Cells and Tissues

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Product

Resources

About

Development of an ¹⁸F-Labeled Irreversible Inhibitor of Transglutaminase 2 as Radiometric Tool for Quantitative Expression Profiling in Cells and Tissues