Peroxidase Enzymes Regulate Collagen Extracellular Matrix Biosynthesis

Mark DeNichilo, Vasilios Panagopoulos, Timothy Rayner, Romana Borowicz, John Greenwood, Andreas Evdokiou

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)

    Abstract

    Myeloperoxidase and eosinophil peroxidase are heme-containing enzymes often physically associated with fibrotic tissue and cancer in various organs, without any direct involvement in promoting fibroblast recruitment and extracellular matrix (ECM) biosynthesis at these sites. We report herein novel findings that show peroxidase enzymes possess a well-conserved profibrogenic capacity to stimulate the migration of fibroblastic cells and promote their ability to secrete collagenous proteins to generate a functional ECM both in vitro and in vivo. Mechanistic studies conducted using cultured fibroblasts show that these cells are capable of rapidly binding and internalizing both myeloperoxidase and eosinophil peroxidase. Peroxidase enzymes stimulate collagen biosynthesis at a post-translational level in a prolyl 4-hydroxylase-dependent manner that does not require ascorbic acid. This response was blocked by the irreversible myeloperoxidase inhibitor 4-amino-benzoic acid hydrazide, indicating peroxidase catalytic activity is essential for collagen biosynthesis. These results suggest that peroxidase enzymes, such as myeloperoxidase and eosinophil peroxidase, may play a fundamental role in regulating the recruitment of fibroblast and the biosynthesis of collagen ECM at sites of normal tissue repair and fibrosis, with enormous implications for many disease states where infiltrating inflammatory cells deposit peroxidases.

    Original languageEnglish
    Article number1979
    Pages (from-to)1372-1384
    Number of pages13
    JournalAmerican Journal of Pathology
    Volume185
    Issue number5
    Early online date7 Mar 2015
    DOIs
    Publication statusPublished - May 2015

    Keywords

    • peroxidase enzymes
    • fibroblastic cells
    • collagen biosynthesis

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