Peroxidasin is secreted and incorporated into the extracellular matrix of myofibroblasts and fibrotic kidney

Zalán Péterfi, Ágnes Donkó, Anna Orient, Adrienn Sum, Ágnes Prókai, Beáta Molnár, Zoltán Veréb, E. Rajnavolgyi, K. Kovács, V. Müller, Attila J. Szabó, M. Geiszt

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Mammalian peroxidases are heme-containing enzymes that serve diverse biological roles, such as host defense and hormone biosynthesis. A mammalian homolog of Drosophila peroxidasin belongs to the peroxidase family; however, its function is currently unknown. In this study, we show that peroxidasin is present in the endoplasmic reticulum of human primary pulmonary and dermal fibroblasts , and the expression of this protein is increased during transforming growth factor-β1-induced myofibroblast differentiation. Myofibroblasts secrete peroxidasin into the extracellular space where it becomes organized into a fibril-like network and colocalizes with fibronectin, thus helping to form the extracellular matrix. We also demonstrate that peroxidasin expression is increased in a murine model of kidney fibrosis and that peroxidasin localizes to the peritubular space in fibrotic kidneys. In addition, we show that this novel pathway of extracellular matrix formation is unlikely mediated by the peroxidase activity of the protein. Our data indicate that peroxidasin secretion represents a previously unknown pathway in extracellular matrix formation with a potentially important role in the physiological and pathological fibrogenic response.

Original languageEnglish
Pages (from-to)725-735
Number of pages11
JournalAmerican Journal of Pathology
Volume175
Issue number2
DOIs
Publication statusPublished - Aug 2009

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Myofibroblasts
Extracellular Matrix
Kidney
Peroxidase
Peroxidases
Extracellular Space
Transforming Growth Factors
Heme
Fibronectins
Endoplasmic Reticulum
Drosophila
peroxidasin
Proteins
Fibrosis
Fibroblasts
Hormones
Lung
Skin
Enzymes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Peroxidasin is secreted and incorporated into the extracellular matrix of myofibroblasts and fibrotic kidney. / Péterfi, Zalán; Donkó, Ágnes; Orient, Anna; Sum, Adrienn; Prókai, Ágnes; Molnár, Beáta; Veréb, Zoltán; Rajnavolgyi, E.; Kovács, K.; Müller, V.; Szabó, Attila J.; Geiszt, M.

In: American Journal of Pathology, Vol. 175, No. 2, 08.2009, p. 725-735.

Research output: Contribution to journalArticle

Péterfi, Zalán ; Donkó, Ágnes ; Orient, Anna ; Sum, Adrienn ; Prókai, Ágnes ; Molnár, Beáta ; Veréb, Zoltán ; Rajnavolgyi, E. ; Kovács, K. ; Müller, V. ; Szabó, Attila J. ; Geiszt, M. / Peroxidasin is secreted and incorporated into the extracellular matrix of myofibroblasts and fibrotic kidney. In: American Journal of Pathology. 2009 ; Vol. 175, No. 2. pp. 725-735.
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