Transglutaminase Enzyme Increase The Ts In Retanning In Leather

Application of TG2 at cartilage interfaces

Increased adhesive strength at cartilage interfaces in vitro

Treatment of cartilage lesions

[95]

Microbial TG

Modification of gelatin and collagen

Increased proliferation of fibroblasts and differentiation of osteoblasts

Scaffolds for wound dressing and tissue repair

[96-98]

TGs represent a new class of wound healing mediators. By targeting this group of enzymes, new healing strategies are under development with promising applications in clinics. The use of TGs has been exploited in a number of different ways: some TG members in purified or recombinant form have been utilized to facilitate healing in a wide range of therapeutic contexts; different TG inhibitors have also been utilized to control fibroproliferative conditions; finally, TGs have also been utilized as biocatalysts, by virtue of the protein cross-linking activity, for the modification of natural polymers e.g. fibrin and gelatin for the development of scaffolds for wound repair using a tissue engineering approach. A short overview of some of the TG-based approaches to wound repair is presented in table 2.

Conclusions

In conclusion the information presented in this chapter indicates that a number of TGs may be associated with the events, which occur during both

Fig. 4. TG2 - a multifunctional role in normal and aberrant wound repair. Exposure of certain cell types to various stress factors causes an upregulation of TG2. If the cell loses Ca2+ homeostasis TG2 becomes activated resulting in the cross-linking of cellular proteins and TG2-associated cell death. This is independent of chromatin cleavage and caspase-3 activity. If the TG2 is released, at the cell surface it may act as an integrin coreceptor in the binding of cells to FN, thus facilitating migration. In addition, it can be deposited into the ECM where once bound to FN it acts as an integrin-independent adhesive protein which binds to cell surface heparan sulphate. Both these roles are independent of transamidating activity. However in the extracellular environment high Ca2+ and low GTP/GDP levels will result in TG2 activation. Once activated it can participate in TGF-p1 activation, deposit ECM components through protein cross-linking employing nonconventional deposition pathways

Fig. 4. TG2 - a multifunctional role in normal and aberrant wound repair. Exposure of certain cell types to various stress factors causes an upregulation of TG2. If the cell loses Ca2+ homeostasis TG2 becomes activated resulting in the cross-linking of cellular proteins and TG2-associated cell death. This is independent of chromatin cleavage and caspase-3 activity. If the TG2 is released, at the cell surface it may act as an integrin coreceptor in the binding of cells to FN, thus facilitating migration. In addition, it can be deposited into the ECM where once bound to FN it acts as an integrin-independent adhesive protein which binds to cell surface heparan sulphate. Both these roles are independent of transamidating activity. However in the extracellular environment high Ca2+ and low GTP/GDP levels will result in TG2 activation. Once activated it can participate in TGF-p1 activation, deposit ECM components through protein cross-linking employing nonconventional deposition pathways normal and aberrant wound healing (fig. 4). Importantly, it confirms that TGs are indeed a new class of wound healing mediators that represent strategic therapeutic targets in the treatment of various diseases. In addition, it demonstrates the growing interest in these enzymes as applied biocatalysts for use as tissue glues, in the production of novel biomaterials for tissue engineering and for facilitating the repair of both soft and hard tissues after disease or injury.

Acknowledgments

The authors would like to thank the EPSRC, the BBSRC, the Wellcome Trust, Diabetes UK, the National Kidney Research Fund for funding the work referred to in this review. They would also like to thank Shakthi Dookie for helping in its preparation.

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Dr. Martin Griffin

School of Life and Health Sciences, Aston University Aston Triangle, B4 7ET, Birmingham (UK)

Tel. +44 121 204 3942, Fax +44 121 359 2677, E-Mail [email protected]

Mehta K, Eckert R (eds): Transglutaminases.

Prog Exp Tum Res. Basel, Karger, 2005, vol 38, pp 115-124

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