Proteomics of serum extracellular vesicles identifies a novel COPD biomarker, fibulin-3 from elastic fibres.

Journal

ERJ open research
ISSN: 2312-0541
Titre abrégé: ERJ Open Res
Pays: England
ID NLM: 101671641

Informations de publication

Date de publication:
Jan 2021
Historique:
received: 10 09 2020
accepted: 18 11 2020
entrez: 29 3 2021
pubmed: 30 3 2021
medline: 30 3 2021
Statut: epublish

Résumé

There is an unmet need for novel biomarkers in the diagnosis of multifactorial COPD. We applied next-generation proteomics to serum extracellular vesicles (EVs) to discover novel COPD biomarkers. EVs from 10 patients with COPD and six healthy controls were analysed by tandem mass tag-based non-targeted proteomics, and those from elastase-treated mouse models of emphysema were also analysed by non-targeted proteomics. For validation, EVs from 23 patients with COPD and 20 healthy controls were validated by targeted proteomics. Using non-targeted proteomics, we identified 406 proteins, 34 of which were significantly upregulated in patients with COPD. Of note, the EV protein signature from patients with COPD reflected inflammation and remodelling. We also identified 63 upregulated candidates from 1956 proteins by analysing EVs isolated from mouse models. Combining human and mouse biomarker candidates, we validated 45 proteins by targeted proteomics, selected reaction monitoring. Notably, levels of fibulin-3, tripeptidyl-peptidase 2, fibulin-1, and soluble scavenger receptor cysteine-rich domain-containing protein were significantly higher in patients with COPD. Moreover, six proteins; fibulin-3, tripeptidyl-peptidase 2, UTP-glucose-1-phosphate uridylyl transferase, CD81, CD177, and oncoprotein-induced transcript 3, were correlated with emphysema. Upregulation of fibulin-3 was confirmed by immunoblotting of EVs and immunohistochemistry in lungs. Strikingly,

Identifiants

DOI: 10.1183/23120541.00658-2020 PMID: 33778046 PMC: PMC7983195
pubmed: 33778046
doi: 10.1183/23120541.00658-2020
pii: 00658-2020
pmc: PMC7983195
pii:
doi:

Types de publication

Journal Article

Langues

eng

Informations de copyright

Copyright ©ERS 2021.

Déclaration de conflit d'intérêts

Conflict of interest: T. Koba has nothing to disclose. Conflict of interest: Y. Takeda has nothing to disclose. Conflict of interest: R. Narumi has nothing to disclose. Conflict of interest: T. Shiromizu has nothing to disclose. Conflict of interest: Y. Nojima has nothing to disclose. Conflict of interest: M. Ito has nothing to disclose. Conflict of interest: M. Kuroyama has nothing to disclose. Conflict of interest: Y. Futami has nothing to disclose. Conflict of interest: T. Takimoto has nothing to disclose. Conflict of interest: T. Matsuki has nothing to disclose. Conflict of interest: R. Edahiro has nothing to disclose. Conflict of interest: S. Nojima has nothing to disclose. Conflict of interest: Y. Hayama has nothing to disclose. Conflict of interest: K. Fukushima has nothing to disclose. Conflict of interest: H. Hirata has nothing to disclose. Conflict of interest: S. Koyama has nothing to disclose. Conflict of interest: K. Iwahori has nothing to disclose. Conflict of interest: I. Nagatomo has nothing to disclose. Conflict of interest: M. Suzuki has nothing to disclose. Conflict of interest: Y. Shirai has nothing to disclose. Conflict of interest: T. Murakami has nothing to disclose. Conflict of interest: K. Nakanishi has nothing to disclose. Conflict of interest: T. Nakatani has nothing to disclose. Conflict of interest: Y. Suga has nothing to disclose. Conflict of interest: K. Miyake has nothing to disclose. Conflict of interest: T. Shiroyama has nothing to disclose. Conflict of interest: H. Kida has nothing to disclose. Conflict of interest: T. Sasaki has nothing to disclose. Conflict of interest: K. Ueda has nothing to disclose. Conflict of interest: K. Mizuguchi has nothing to disclose. Conflict of interest: J. Adachi has nothing to disclose. Conflict of interest: T. Tomonaga has nothing to disclose. Conflict of interest: A. Kumanogoh has nothing to disclose.

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Auteurs

Taro Koba (T)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
ORCID: 0000-0001-7715-9042

Yoshito Takeda (Y)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Ryohei Narumi (R)

Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.

Takashi Shiromizu (T)

Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.

Yosui Nojima (Y)

Laboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
ORCID: 0000-0002-6821-0093

Mari Ito (M)

Laboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.

Muneyoshi Kuroyama (M)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Yu Futami (Y)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Takayuki Takimoto (T)

Dept of Respiratory Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Kita-Ku, Sakai, Osaka, Japan.

Takanori Matsuki (T)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Ryuya Edahiro (R)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Satoshi Nojima (S)

Dept of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Yoshitomo Hayama (Y)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Kiyoharu Fukushima (K)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Haruhiko Hirata (H)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Shohei Koyama (S)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Kota Iwahori (K)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Izumi Nagatomo (I)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Mayumi Suzuki (M)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Yuya Shirai (Y)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Teruaki Murakami (T)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Kaori Nakanishi (K)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
ORCID: 0000-0002-4153-5277

Takeshi Nakatani (T)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Yasuhiko Suga (Y)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Kotaro Miyake (K)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Takayuki Shiroyama (T)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Hiroshi Kida (H)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
ORCID: 0000-0002-9351-7855

Takako Sasaki (T)

Dept of Biochemistry II, Faculty of Medicine, Oita University, Yufu, Oita, Japan.

Koji Ueda (K)

Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Koto, Tokyo, Japan.

Kenji Mizuguchi (K)

Laboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.

Jun Adachi (J)

Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.

Takeshi Tomonaga (T)

Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.

Atsushi Kumanogoh (A)

Dept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Classifications MeSH