Transglutaminases in Wound Healing: Crosslinking of Fibrin and Collagen proteins скачать в хорошем качестве

Transglutaminases in Wound Healing: Crosslinking of Fibrin and Collagen proteins

http://webs.ono.com/fotgcren/index.htm TELCI 2006 Tissue transglutaminase (TG2) - a wound response enzyme Telci G, Griffin M (2006) Tissue transglutaminase (TG2)-a wound response enzyme. Front Biosci 11: 867–882. Wound healing begins immediately after injury progressing through the complex phases of blood clotting, inflammation, new tissue formation, and finally tissue remodeling. Particular members of the transglutaminase (TG) family are upregulated during wound healing and act as a novel class of wound-healing mediators during the repair process. This group of enzymes which crosslink proteins via epsilon(gamma-glutamyl) lysine bridges are involved in wound healing through their ability to stabilize proteins. Numerous studies have provided significant evidence for the importance of transglutaminases during these tissue repair episodes. Identification of TG2-mediated epsilon(gamma-glutamyl) lysine cross-links during the different stages of the dermal tissue repair process and the presentation of impaired dermal-wound healing in TG2-deficient mice define an important role for TG2 in wound healing biology. Early studies with animal models reported increased TG2 expression and activity following cutanous wounding. In these experiments, detectable levels of TG2 antigen and activity were found in endothelial cells, macrophages, and skeletal muscle cells throughout the different stages of the healing process. The secretion of TG2 in response to injury has been also revealed at the cellular level. Time course analysis of in situ TG2 activity in scratch-wounded cell monolayers of fibroblasts and epithelial-like cells demonstrated a dramatic increase in TG2-mediated cross-links at the edge of the wound bed. In support of a role for TG2 in matrix stabilization, TG2-mediated cross-linking was detected in the both provisional matrix and new granulation tissue of punch biopsy wounds. Nicholas et al. reported a dramatic increase in TG2 transamidating activity in the ECM of mechanically wounded monolayers of fibroblasts induced to over-express TG2. In addition to the ECM, increases in intracellular TG2 levels and TG2 cross-linking activity at the edge of the wound bed suggested the stabilization of the wound area by enhancing matrix strength and/or valency. The general picture that emerges from these studies is that TG2-mediated cross-linking reactions results in the rapid stabilization and modulation of the matrix in the immediate wound area, which further promotes subsequent wound healing by promoting matrix accumulation and regulating cell proliferation and migration. BLOOD CLOT: TGASE FIBRIN CROSSLINKING Initial response to injury; Hemostasis Tissue injury activates the blood coagulation cascade, leading to the formation of the blood clot which rapidly fills the wound site. Upon injury, subendothelial tissue factor is exposed to the blood flow, which initiates a series of zymogen activation reactions, resulting in thrombin-mediated conversion of soluble fibrinogen into insoluble fibrin monomers. During these final stages of the cascade, the A subunit of Factor XIII (Factor XIIIA) is activated to Factor XIIIa (plasma transglutaminase) by thrombin, which catalyzes a transamidation reaction initially resulting in the cross-linking of the gamma-chains on adjacent fibrin monomers. The cross-linking of fibrin is of utmost importance not only to stem the loss of blood but to provide a network for cell migration and new tissue formation. The cross-linking of alpha-chain polymers and alpha-gamma heteromers are catalyzed more slowly by Factor XIIIa, which then gives the clot additional strength. GRANULATION TISSUE: TGASE COLLAGEN CROSSLINKING Proliferation & Remodeling: The proliferation and migration of fibroblast to the wound site results in replacement of the provisional matrix with granulation tissue consisting mainly of fibronectin (FN) and collagen. During remodeling, collagen becomes organized into large bundles facilitating intramolecular and intermolecular collagen cross-links. TG2 actively participates in cross-linking a number of different types of collagen including II, III V, VII and XI and more recently collagen type I. In rhabdomyosarcoma cells, TG2 can catalyse lysyl oxidase independent cross-linking within collagen V and XI, leading to covalent stabilization of the collagen matrix. Copyright Disclaimer Under Section 107 of the Copyright Act 1976, allowance is made for "fair use" for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. Fair use is a use permitted by copyright statute that might otherwise be infringing. Non-profit, educational or personal use tips the balance in favor of fair use