Peroxidasin is secreted and incorporated into the extracellular matrix of myofibroblasts and fibrotic kidney.
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-beta1-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.
Péterfi
Zalán
Z
Department of Physiology, Semmelweis University, Faculty of Medicine, PO Box 259 H-1444 Buda-pest, Hungary.
Donkó
Agnes
A
Orient
Anna
A
Sum
Adrienn
A
Prókai
Agnes
A
Molnár
Beáta
B
Veréb
Zoltán
Z
Rajnavölgyi
Eva
E
Kovács
Krisztina J
KJ
Müller
Veronika
V
Szabó
Attila J
AJ
Geiszt
Miklós
M
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D000097423:Peroxidasin
D016326:Extracellular Matrix Proteins; D009195:Peroxidase; D000097423:Peroxidasin