Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis

Chiara Dianzani, Elena Bellavista, Juliane Liepe, Claudia Verderio, Morena Martucci, Aurelia Santoro, Annalisa Chiocchetti, Casimiro Luca Gigliotti, Elena Boggio, Benedetta Ferrara, Loredana Riganti, Christin Keller, Katharina Janek, Agathe Niewienda, Chiara Fenoglio, Melissa Sorosina, Roberto Cantello, Peter M Kloetzel, Michael P H Stumpf, Friedemann PaulKlemens Ruprecht, Daniela Galimberti, Filippo Martinelli Boneschi, Cristoforo Comi, Umberto Dianzani, Michele Mishto

Research output: Contribution to journalArticlepeer-review

Abstract

Osteopontin is a pleiotropic cytokine that is involved in several diseases including multiple sclerosis. Secreted osteopontin is cleaved by few known proteases, modulating its pro-inflammatory activities. Here we show by in vitro experiments that secreted osteopontin can be processed by extracellular proteasomes, thereby producing fragments with novel chemotactic activity. Furthermore, osteopontin reduces the release of proteasomes in the extracellular space. The latter phenomenon seems to occur in vivo in multiple sclerosis, where it reflects the remission/relapse alternation. The extracellular proteasome-mediated inflammatory pathway may represent a general mechanism to control inflammation in inflammatory diseases.

Original languageEnglish
Article number43718
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Mar 9 2017

Keywords

  • Journal Article

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