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Matrix metalloproteinase degradomics at the epidermal-dermal interface

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Facilitating research on MMP-10

EU-funded researchers have modified a mass spectrometry-based technology called terminal amine isotopic labelling of substrates (TAILS) to study the matrix metalloproteinase (MMP)-10 enzyme.

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The MMP-10 enzyme degrades proteins present in the extracellular matrix (ECM) and facilitates migration of skin cells to sites of injury to promote healing. Unfortunately, recent research activities have also uncovered its role in the pathogenesis of skin cancer. However, the underlying mechanisms of MMP-10 in normal and pathological conditions are still to a large extent a mystery. Scientists of the project 'Matrix metalloproteinase degradomics at the epidermal-dermal interface' (SKINTERMINOMICS) modified TAILS to identify new protease substrates and monitor their cleavage activity over time. This innovative technique enables the study of such proteases in multiple physiological conditions within the same experiment. Researchers successfully applied TAILS for the study of MMP-10 substrates and identified previously unknown MMP-10–dependent cleavages of ECM proteins. The proteins cleaved included type I collagen, ADAMTS-like protein 1 (ADAMTSL1) and platelet-derived growth factor receptor alpha (PDGFRalpha). The role of these proteins in healing skin wounds and skin tumours is currently being studied. Application of TAILS on a mouse model of cutaneous wound healing helped identify different proteases that are responsible for specific protein cleavages during healing. The study of the functions of specific protease–substrate combinations is currently underway. Project activities have laid the foundation for study of proteases and their function using novel cutting-edge techniques. The ensuing flurry of research activities should help in identification of novel targets of therapy to promote wound healing and arrest cancer.

Keywords

MMP-10, mass spectrometry, terminal amine isotopic labelling of substrates, matrix metalloproteinase-10, enzyme, proteases

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