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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 4/2013

Open Access 01-08-2013 | Research article

Versican is upregulated in circulating monocytes in patients with systemic sclerosis and amplifies a CCL2-mediated pathogenic loop

Authors: Ayako Masuda, Hidekata Yasuoka, Takashi Satoh, Yuka Okazaki, Yukie Yamaguchi, Masataka Kuwana

Published in: Arthritis Research & Therapy | Issue 4/2013

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Abstract

Introduction

Altered phenotypes of circulating monocytes of patients with systemic sclerosis (SSc) have been reported, but the role of these alterations in the pathogenesis of SSc remains unclear. This study was undertaken to identify molecules that are preferentially expressed by SSc monocytes, and to investigate the roles of these molecules in the pathogenic process of SSc.

Methods

We analyzed circulating CD14+ monocytes isolated from 36 patients with SSc and 32 healthy control subjects. The monocytes' gene expression profiles were assessed by Oligo GEArray® (SABiosciences, Frederic, MA, USA) and semiquantitative or quantitative PCR; their protein expression was evaluated in culture supernatants of unstimulated monocytes by immunoblotting or ELISA, and by immunocytostaining. Monocyte chemoattractant activity of CCL2 was assessed in a TransWell® system (Corning Incorporated, Corning, NY, USA) in the presence or absence of chondroitin sulfate (CS).

Results

A step-wise approach to profiling gene expression identified that versican and CCL2 were upregulated in SSc monocytes. Subsequent analysis of proteins expressed in monocyte culture supernatants confirmed enhanced production of versican and CCL2 in SSc monocytes compared with control monocytes. CCL2 bound to CS chains of versican and colocalized with versican in the monocytes' Golgi apparatus. Finally, CCL2 had a greater ability to mediate monocyte migration when bound to CS chains, because this binding provided efficient formation of CCL2 gradients and protection from protease attack.

Conclusion

Circulating monocytes with elevated versican and CCL2 levels may contribute to the fibrotic process in a subset of SSc patients by amplifying a positive feedback loop consisting of versican, CCL2, and the influx of monocytes.
Appendix
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Metadata
Title
Versican is upregulated in circulating monocytes in patients with systemic sclerosis and amplifies a CCL2-mediated pathogenic loop
Authors
Ayako Masuda
Hidekata Yasuoka
Takashi Satoh
Yuka Okazaki
Yukie Yamaguchi
Masataka Kuwana
Publication date
01-08-2013
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2013
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4251

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