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Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis

Research output: Contribution to journalArticle

Chiara Dianzani, Domizia Vecchio, Nausicaa Clemente, Annalisa Chiocchetti, Filippo Martinelli Boneschi, Daniela Galimberti, Umberto Dianzani, Cristoforo Comi, Michele Mishto, Juliane Liepe

Original languageEnglish
JournalCells
Volume8
Issue number3
DOIs
Accepted/In press18 Mar 2019
Published20 Mar 2019

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Abstract

The function of proteasomes in extracellular space is still largely unknown. The extracellular proteasome-osteopontin circuit has recently been hypothesized to be part of the inflammatory machinery regulating relapse/remission phase alternation in multiple sclerosis. However, it is still unclear what dynamics there are between the different elements of the circuit, what the role of proteasome isoforms is, and whether these inflammatory circuit dynamics are associated with the clinical severity of multiple sclerosis. To shed light on these aspects of this novel inflammatory circuit, we integrated in vitro proteasome isoform data, cell chemotaxis cell culture data, and clinical data of multiple sclerosis cohorts in a coherent computational inference framework. Thereby, we modeled extracellular osteopontin-proteasome circuit dynamics during relapse/remission alternation in multiple sclerosis. Applying this computational framework to a longitudinal study on single multiple sclerosis patients suggests a complex interaction between extracellular proteasome isoforms and osteopontin with potential clinical implications.

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