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

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Item Type:Article
Title:Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis
Creators Name:Dianzani, C. and Bellavista, E. and Liepe, J. and Verderio, Cl. and Martucci, M. and Santoro, A. and Chiocchetti, A. and Luca Gigliotti, C. and Boggio, E. and Ferrara, B. and Riganti, L. and Keller, C. and Janek, K. and Niewienda, A. and Fenoglio, C. and Sorosina, M. and Cantello, R. and Kloetzel, P.M. and Stumpf, M.P.H. and Paul, F. and Ruprecht, K. and Galimberti, D. and Martinelli Boneschi, F. and Comi, C. and Dianzani, U. and Mishto, M.
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.
Keywords:Amino Acid Sequence, Chemotaxis, Endothelial Cells, Extracellular Space, Extracellular Vesicles, Lymphocytes, Molecular, Models, Multiple Sclerosis, Osteopontin, Proteasome Endopeptidase Complex, Protein Conformation, Structure-Activity Relationship
Source:Scientific Reports
ISSN:2045-2322
Publisher:Nature Publishing Group (U.K.)
Volume:7
Page Range:43718
Date:9 March 2017
Official Publication:https://doi.org/10.1038/srep43718
PubMed:View item in PubMed

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