Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalCells
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 20 2019

Fingerprint

Osteopontin
Proteasome Endopeptidase Complex
Multiple Sclerosis
Networks (circuits)
Protein Isoforms
Recurrence
Extracellular Space
Chemotaxis
Cell culture
Machinery
Integrated circuits
Longitudinal Studies
Cell Culture Techniques

Cite this

Dianzani, C., Vecchio, D., Clemente, N., Chiocchetti, A., Martinelli Boneschi, F., Galimberti, D., ... Liepe, J. (2019). Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis. Cells, 8(3). https://doi.org/10.3390/cells8030262

Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis. / Dianzani, Chiara; Vecchio, Domizia; Clemente, Nausicaa; Chiocchetti, Annalisa; Martinelli Boneschi, Filippo; Galimberti, Daniela; Dianzani, Umberto; Comi, Cristoforo; Mishto, Michele; Liepe, Juliane.

In: Cells, Vol. 8, No. 3, 20.03.2019.

Research output: Contribution to journalArticle

Dianzani, C, Vecchio, D, Clemente, N, Chiocchetti, A, Martinelli Boneschi, F, Galimberti, D, Dianzani, U, Comi, C, Mishto, M & Liepe, J 2019, 'Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis', Cells, vol. 8, no. 3. https://doi.org/10.3390/cells8030262
Dianzani C, Vecchio D, Clemente N, Chiocchetti A, Martinelli Boneschi F, Galimberti D et al. Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis. Cells. 2019 Mar 20;8(3). https://doi.org/10.3390/cells8030262
Dianzani, Chiara ; Vecchio, Domizia ; Clemente, Nausicaa ; Chiocchetti, Annalisa ; Martinelli Boneschi, Filippo ; Galimberti, Daniela ; Dianzani, Umberto ; Comi, Cristoforo ; Mishto, Michele ; Liepe, Juliane. / Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis. In: Cells. 2019 ; Vol. 8, No. 3.
@article{cd27bacf35fb4d4aa4b8aeeb4b7c4acf,
title = "Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis",
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.",
author = "Chiara Dianzani and Domizia Vecchio and Nausicaa Clemente and Annalisa Chiocchetti and {Martinelli Boneschi}, Filippo and Daniela Galimberti and Umberto Dianzani and Cristoforo Comi and Michele Mishto and Juliane Liepe",
year = "2019",
month = "3",
day = "20",
doi = "10.3390/cells8030262",
language = "English",
volume = "8",
journal = "Cells",
issn = "2073-4409",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",

}

TY - JOUR

T1 - Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis

AU - Dianzani, Chiara

AU - Vecchio, Domizia

AU - Clemente, Nausicaa

AU - Chiocchetti, Annalisa

AU - Martinelli Boneschi, Filippo

AU - Galimberti, Daniela

AU - Dianzani, Umberto

AU - Comi, Cristoforo

AU - Mishto, Michele

AU - Liepe, Juliane

PY - 2019/3/20

Y1 - 2019/3/20

N2 - 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.

AB - 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.

U2 - 10.3390/cells8030262

DO - 10.3390/cells8030262

M3 - Article

C2 - 30897778

VL - 8

JO - Cells

JF - Cells

SN - 2073-4409

IS - 3

ER -