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 Paul; Klemens Ruprecht; Daniela Galimberti; Filippo Martinelli Boneschi; Cristoforo Comi; Umberto Dianzani; Michele Mishto

doi:10.1038/srep43718

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 journal › Article › peer-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 language	English
Article number	43718
Journal	Scientific Reports
Volume	7
DOIs	https://doi.org/10.1038/srep43718
Publication status	Published - 9 Mar 2017

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Dianzani, C., Bellavista, E., Liepe, J., Verderio, C., Martucci, M., Santoro, A., Chiocchetti, A., Gigliotti, C. L., Boggio, E., Ferrara, B., Riganti, L., Keller, C., Janek, K., Niewienda, A., Fenoglio, C., Sorosina, M., Cantello, R., Kloetzel, P. M., Stumpf, M. P. H., ... Mishto, M. (2017). Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis. Scientific Reports, 7, Article 43718. https://doi.org/10.1038/srep43718

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title = "Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis",

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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

month = mar,

day = "9",

doi = "10.1038/srep43718",

language = "English",

volume = "7",

journal = "Scientific Reports",

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Dianzani, C, Bellavista, E, Liepe, J, Verderio, C, Martucci, M, Santoro, A, Chiocchetti, A, Gigliotti, CL, Boggio, E, Ferrara, B, Riganti, L, Keller, C, Janek, K, Niewienda, A, Fenoglio, C, Sorosina, M, Cantello, R, Kloetzel, PM, Stumpf, MPH, Paul, F, Ruprecht, K, Galimberti, D, Boneschi, FM, Comi, C , Dianzani, U & Mishto, M 2017, 'Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis', Scientific Reports, vol. 7, 43718. https://doi.org/10.1038/srep43718

TY - JOUR

T1 - Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis

AU - Dianzani, Chiara

AU - Bellavista, Elena

AU - Liepe, Juliane

AU - Verderio, Claudia

AU - Martucci, Morena

AU - Santoro, Aurelia

AU - Chiocchetti, Annalisa

AU - Gigliotti, Casimiro Luca

AU - Boggio, Elena

AU - Ferrara, Benedetta

AU - Riganti, Loredana

AU - Keller, Christin

AU - Janek, Katharina

AU - Niewienda, Agathe

AU - Fenoglio, Chiara

AU - Sorosina, Melissa

AU - Cantello, Roberto

AU - Kloetzel, Peter M.

AU - Stumpf, Michael P.H.

AU - Paul, Friedemann

AU - Ruprecht, Klemens

AU - Galimberti, Daniela

AU - Boneschi, Filippo Martinelli

AU - Comi, Cristoforo

AU - Dianzani, Umberto

AU - Mishto, Michele

PY - 2017/3/9

Y1 - 2017/3/9

N2 - 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.

AB - 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.

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U2 - 10.1038/srep43718

DO - 10.1038/srep43718

M3 - Article

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 43718

ER -

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

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