Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis

Shirai, Yuya; Enomoto, Takatoshi; Takeda, Yoshito; Edahiro, Ryuya; Takahashi-Itoh, Miho; Noda, Yoshimi; Adachi, Yuichi; Nakayama, Mana; Kawasaki, Takahiro; Koba, Taro; Futami, Yu; Yoshimura, Hanako; Amiya, Saori; Hara, Reina; Yamamoto, Makoto; Nakatsubo, Daisuke; Suga, Yasuhiko; Naito, Maiko; Masuhiro, Kentaro; Matsuki, Takanori; Hirata, Haruhiko; Iwahori, Kota; Nagatomo, Izumi; Miyake, Kotaro; Koyama, Shohei; Fukushima, Kiyoharu; Shiroyama, Takayuki; Naito, Yujiro; Futami, Shinji; Natsume-Kitatani, Yayoi; Ose, Naoko; Funaki, Soichiro; Nojima, Satoshi; Shichino, Shigeyuki; Yanagawa, Masahiro; Shintani, Yasushi; Nogami-Itoh, Mari; Adachi, Jun; Inoue, Yoshikazu; Tomonaga, Takeshi; Okada, Yukinori; Mizuguchi, Kenji; Kumanogoh, Atsushi

doi:https://doi.org/10.1186/s12967-025-07011-2

Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis

Shirai, Yuya; Enomoto, Takatoshi; Takeda, Yoshito et al.

Journal of Translational Medicine, 2025, 23, 1102

Number of Access:490（2026-02-04 09:37 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/103502

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Title	Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis
Creator	NRID 1000050899945 1000050899945 ORCID 0000-0002-0518-9020 0000-0002-0518-9020 researchmap permalink yuyashirai yuyashirai Scopus Author ID 58966287700 58966287700 CreatorName Shirai, Yuya
	NRID 1000091022036 1000091022036 ORCID 0000-0002-1771-6684 0000-0002-1771-6684 researchmap permalink enomoto-takatoshi enomoto-takatoshi Scopus Author ID 57212756610 57212756610 CreatorName Enomoto, Takatoshi
	NRID 1000040452388 1000040452388 researchmap permalink yoshi10 yoshi10 Scopus Author ID 7404001848 7404001848 CreatorName Takeda, Yoshito
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	CreatorName Takahashi-Itoh, Miho
	CreatorName Noda, Yoshimi
	CreatorName Adachi, Yuichi
	CreatorName Nakayama, Mana
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	CreatorName Koba, Taro
	NRID 1000040836409 1000040836409 CreatorName Futami, Yu
	CreatorName Yoshimura, Hanako
	CreatorName Amiya, Saori
	CreatorName Hara, Reina
	CreatorName Yamamoto, Makoto
	CreatorName Nakatsubo, Daisuke
	NRID 1000060895069 1000060895069 CreatorName Suga, Yasuhiko
	NRID 1000010974686 1000010974686 researchmap permalink maikonaito maikonaito CreatorName Naito, Maiko
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	CreatorName Matsuki, Takanori
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	CreatorName Nagatomo, Izumi
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	CreatorName Futami, Shinji
	CreatorName Natsume-Kitatani, Yayoi
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	CreatorName Nogami-Itoh, Mari
	NRID 1000020437255 1000020437255 CreatorName Adachi, Jun
	NRID 1000090240895 1000090240895 CreatorName Inoue, Yoshikazu
	NRID 1000080227644 1000080227644 CreatorName Tomonaga, Takeshi
	NRID 1000070727411 1000070727411 ORCID 0000-0002-0311-8472 0000-0002-0311-8472 researchmap permalink yokada yokada Scopus Author ID 7005443464 7005443464 CreatorName Okada, Yukinori
	NRID 1000050450896 1000050450896 ORCID 0000-0003-3021-7078 0000-0003-3021-7078 researchmap permalink kenji_mizuguchi kenji_mizuguchi Scopus Author ID 57191477452 57191477452 CreatorName Mizuguchi, Kenji
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Subject	Extracellular vesicles
	Idiopathic pulmonary fibrosis
	Non-target proteomics
	SFTPB
Description	Shirai Y., Enomoto T., Takeda Y., et al. Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis. Journal of Translational Medicine 23, 1102 (2025); https://doi.org/10.1186/s12967-025-07011-2.
Abstract	Background: Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease caused by an interplay of genetic and environmental factors. Biomarkers that reflect the progression of fibrosis are required for the management of IPF. Methods: We extracted serum extracellular vesicles from a discovery cohort (127 IPF patients and 34 controls) and a validation cohort (20 IPF patients and 22 controls). Non-targeted proteomic analysis was performed by a data-independent acquisition method. We investigated the proteomic profiles in relation to multiple clinical parameters associated with IPF. To further evaluate the biological relevance of the identified biomarkers, we analyzed publicly available single-cell RNA sequencing datasets of lung tissue and conducted immunochemical validation using our collected lung samples. Results: We obtained 2420 protein profiles in serum extracellular vesicles and identified 19 IPF-associated proteins; their expressions were significantly lung-specific. Protein module analyses revealed that the upstream components of the complement system were increased in IPF. These IPF-associated proteins were involved in various IPF-associated genes and heterogeneously increased in IPF patients. Notably, surfactant protein B (SFTPB) not only showed superior diagnostic performance over the existing marker but was also significantly associated with progressive disease activity, such as the extent of fibrosis and decline in lung function. Furthermore, single-cell RNA-sequencing analysis revealed that SFTPB was associated with the TGF-β/SMAD pathway in SCGB3A2 + cells in IPF lungs. SFTPB expression in SCGB3A2 + cells was confirmed by immunostaining. Conclusions: Serum extracellular vesicles could capture heterogenetic fibrotic profiles in IPF, and SFTPB can be a promising biomarker reflecting the disease activity.
Publisher	BioMed Central Ltd
Source Title	Journal of Translational Medicine
Volume (Issue)	23
Page	1102
Date of Issued	2025-10-15
Language	English
Handle URL	https://hdl.handle.net/11094/103502
eISSN	14795876
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1186/s12967-025-07011-2
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Translational Medicine. 2025, 23, p. 1102
DC.title	Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis
DC.creator	Shirai, Yuya
	Enomoto, Takatoshi
	Takeda, Yoshito
	Edahiro, Ryuya
	Takahashi-Itoh, Miho
	Noda, Yoshimi
	Adachi, Yuichi
	Nakayama, Mana
	Kawasaki, Takahiro
	Koba, Taro
	Futami, Yu
	Yoshimura, Hanako
	Amiya, Saori
	Hara, Reina
	Yamamoto, Makoto
	Nakatsubo, Daisuke
	Suga, Yasuhiko
	Naito, Maiko
	Masuhiro, Kentaro
	Matsuki, Takanori
	Hirata, Haruhiko
	Iwahori, Kota
	Nagatomo, Izumi
	Miyake, Kotaro
	Koyama, Shohei
	Fukushima, Kiyoharu
	Shiroyama, Takayuki
	Naito, Yujiro
	Futami, Shinji
	Natsume-Kitatani, Yayoi
	Ose, Naoko
	Funaki, Soichiro
	Nojima, Satoshi
	Shichino, Shigeyuki
	Yanagawa, Masahiro
	Shintani, Yasushi
	Nogami-Itoh, Mari
	Adachi, Jun
	Inoue, Yoshikazu
	Tomonaga, Takeshi
	Okada, Yukinori
	Mizuguchi, Kenji
	Kumanogoh, Atsushi
DC.publisher	BioMed Central Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-10-15
DC.identifier	https://doi.org/10.1186/s12967-025-07011-2
DC.subject	Extracellular vesicles
	Idiopathic pulmonary fibrosis
	Non-target proteomics
	SFTPB
DC.description	Shirai Y., Enomoto T., Takeda Y., et al. Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis. Journal of Translational Medicine 23, 1102 (2025); https://doi.org/10.1186/s12967-025-07011-2.
DCTERMS.abstract	Background: Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease caused by an interplay of genetic and environmental factors. Biomarkers that reflect the progression of fibrosis are required for the management of IPF. Methods: We extracted serum extracellular vesicles from a discovery cohort (127 IPF patients and 34 controls) and a validation cohort (20 IPF patients and 22 controls). Non-targeted proteomic analysis was performed by a data-independent acquisition method. We investigated the proteomic profiles in relation to multiple clinical parameters associated with IPF. To further evaluate the biological relevance of the identified biomarkers, we analyzed publicly available single-cell RNA sequencing datasets of lung tissue and conducted immunochemical validation using our collected lung samples. Results: We obtained 2420 protein profiles in serum extracellular vesicles and identified 19 IPF-associated proteins; their expressions were significantly lung-specific. Protein module analyses revealed that the upstream components of the complement system were increased in IPF. These IPF-associated proteins were involved in various IPF-associated genes and heterogeneously increased in IPF patients. Notably, surfactant protein B (SFTPB) not only showed superior diagnostic performance over the existing marker but was also significantly associated with progressive disease activity, such as the extent of fibrosis and decline in lung function. Furthermore, single-cell RNA-sequencing analysis revealed that SFTPB was associated with the TGF-β/SMAD pathway in SCGB3A2 + cells in IPF lungs. SFTPB expression in SCGB3A2 + cells was confirmed by immunostaining. Conclusions: Serum extracellular vesicles could capture heterogenetic fibrotic profiles in IPF, and SFTPB can be a promising biomarker reflecting the disease activity.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	103502
citation_title	Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis
citation_author	Shirai, Yuya
	Enomoto, Takatoshi
	Takeda, Yoshito
	Edahiro, Ryuya
	Takahashi-Itoh, Miho
	Noda, Yoshimi
	Adachi, Yuichi
	Nakayama, Mana
	Kawasaki, Takahiro
	Koba, Taro
	Futami, Yu
	Yoshimura, Hanako
	Amiya, Saori
	Hara, Reina
	Yamamoto, Makoto
	Nakatsubo, Daisuke
	Suga, Yasuhiko
	Naito, Maiko
	Masuhiro, Kentaro
	Matsuki, Takanori
	Hirata, Haruhiko
	Iwahori, Kota
	Nagatomo, Izumi
	Miyake, Kotaro
	Koyama, Shohei
	Fukushima, Kiyoharu
	Shiroyama, Takayuki
	Naito, Yujiro
	Futami, Shinji
	Natsume-Kitatani, Yayoi
	Ose, Naoko
	Funaki, Soichiro
	Nojima, Satoshi
	Shichino, Shigeyuki
	Yanagawa, Masahiro
	Shintani, Yasushi
	Nogami-Itoh, Mari
	Adachi, Jun
	Inoue, Yoshikazu
	Tomonaga, Takeshi
	Okada, Yukinori
	Mizuguchi, Kenji
	Kumanogoh, Atsushi
citation_publisher	BioMed Central Ltd
citation_language	English
citation_date	2025-10-15
citation_journal_title	Journal of Translational Medicine
citation_volume	23
citation_firstpage	1102
citation_doi	https://doi.org/10.1186/s12967-025-07011-2
citation_public_url	https://hdl.handle.net/11094/103502

Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis

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