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Transglutaminases: new target molecules for inflammatory bowel disease?
  1. B Siegmund,
  2. M Zeitz
  1. Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik I, Berlin, Germany
  1. Correspondence to:
    Dr B Siegmund
    Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik I, Hindenburgdamm 30, 12200 Berlin, Germany; britta.siegmundcharite.de

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Transglutaminases may be involved in intestinal inflammation and may even represent therapeutic targets for ulcerative colitis

The family of transglutaminases (TG) includes the plasma form factor XIIIa as well as the tissue transglutaminase (tTG) and keratinocyte transglutaminase (TGk). In particular, tTG reminds every gastroenterologist primarily of coeliac disease where tTG represents the key autoantigen.1 Disease induction is confined to tTG, a ubiquitous enzyme which is released from fibroblasts, endothelial, and inflammatory cells during mechanical irritation or inflammation. At acidic pH, which occurs with inflammation, tTG can, apart from its physiological function described in more detail below, also simply deamidate some of the glutamine residues of the gluten peptides. In coeliac disease, deamidation introduces a negative charge into the gluten peptides which can increase the binding affinity to HLA-DQ2 or HLA-DQ8, the primary HLA association in coeliac disease. Binding of gluten peptide to either HLA-DQ2 or HLA-DQ8 results in an increase in their capacity to stimulate T cells, thus inducing intestinal inflammation.2,3

As indicated in this issue of Gut by D’Argenio and colleagues,4 TG may be involved in intestinal inflammation in a completely different way and may even represent a therapeutic target (see page 496). But how can the physiological function of TG be defined? TG are enzymes catalysing the covalent cross linking between proteins by forming ε(γ-glutamyl)-lysine isopeptide bonds. These bonds are formed between glutaminase and lysine residues thus stabilising intra- and extracellular proteins, a process which is required for a variety of essential physiological purposes such as barrier function in epithelia, apoptosis, and extracellular matrix formation.5 Substrates include intracellular (actin cytoskeleton, histones) as well as extracellular (collagen, vitronectin, fibronectin) …

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