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Proteases and Fibrosis

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Proteases and Their Receptors in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

Protein turnover, orchestrated by a large array of proteases, protein complexes, and organelles consumes one-fifth of the human energy. In many diseases this homeostasis is lost resulting in loss of tissue function. One such group of diseases are the fibrotic disorders in which there is progressive fibroproliferation and extracellular matrix deposition. The causes of these diseases are sometimes identified, but often they are cryptic. In any case it is clear that there are shared pathways and processes leading to fibrosis in different tissues such as liver, lung, and kidney. There are also intense efforts to discover ways to inhibit the pathways that lead to fibrosis. Proteases of all classes are known to play roles in fibrosis. The matrix metalloproteases (MMPs) and their inhibitors (the tissue inhibitors of metalloproteinases, TIMPS) can degrade all extracellular matrix components and are thought to be central to pathogenesis. However, cysteine and serine proteases (including caspases, cathepsins, coagulation cascade proteases, and mast cell proteases) are also thought to regulate key processes and cell functions in fibrosis, including extracellular matrix gene expression, cell proliferation, cell apoptosis, epithelial mesenchymal transduction, and fibrocyte recruitment. The multiple pathways and range of proteases involved clearly provides challenges for therapy but it is not surprising that regulation of protease activity and the cell functions they control are being explored as potential targets to treat fibrotic disorders.

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Authors and Affiliations

  1. Centre for Respiratory Research, University College London, 5 University Street, London, WC1E 6JF, UK

    Melissa Heightman & Geoffrey J. Laurent

  2. Immunology Research, Centocor R&D Inc., 145 King of Prussia Road, Radnor, PA, 19087, USA

    Tatiana Ort & Ken Kilgore

  3. Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Welsh & McKean Roads, Spring House, Montgomery, PA, 19477-0776, USA

    Lawrence de Garavilla

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  1. Melissa Heightman
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  2. Tatiana Ort
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  3. Lawrence de Garavilla
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  4. Ken Kilgore
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  5. Geoffrey J. Laurent
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Correspondence to Geoffrey J. Laurent .

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  1. CHU Purpan, INSERM U 563, BP 3028, Toulouse Cedex, 31024, France

    Nathalie Vergnolle

  2. Institut Pasteur, Unite de Defense Innee et Inflammation, INSERM U 874, Rue du Dr. Roux 25, Paris Cedex 15, 75724, France

    Michel Chignard

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Heightman, M., Ort, T., de Garavilla, L., Kilgore, K., Laurent, G.J. (2011). Proteases and Fibrosis. In: Vergnolle, N., Chignard, M. (eds) Proteases and Their Receptors in Inflammation. Progress in Inflammation Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0157-7_7

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