2024年6月17日 / 最終更新日 : 2024年6月17日 ad_y ニュース

2024年 新着論文 33　バイオインフォマティクス分野から論文が発表されました

SFTPB in serum extracellular vesicles as a biomarker of progressive pulmonary fibrosis

JCI Insight. 2024 Jun 10;9(11):e177937. doi: 10.1172/jci.insight.177937.

Authors

Takatoshi Enomoto  1 , Yuya Shirai  1   2 , Yoshito Takeda  1 , Ryuya Edahiro  1   2 , Shigeyuki Shichino  3 , Mana Nakayama  1 , Miho Takahashi-Itoh  1 , Yoshimi Noda  1 , Yuichi Adachi  1 , Takahiro Kawasaki  1 , Taro Koba  1 , Yu Futami  1   4 , Moto Yaga  1 , Yuki Hosono  1 , Hanako Yoshimura  1 , Saori Amiya  1 , Reina Hara  1 , Makoto Yamamoto  1 , Daisuke Nakatsubo  1 , Yasuhiko Suga  1 , Maiko Naito  1 , Kentaro Masuhiro  1 , Haruhiko Hirata  1 , Kota Iwahori  1 , Izumi Nagatomo  1 , Kotaro Miyake  1 , Shohei Koyama  1 , Kiyoharu Fukushima  1 , Takayuki Shiroyama  1 , Yujiro Naito  1 , Shinji Futami  1 , Yayoi Natsume-Kitatani  5   6 , Satoshi Nojima  7 , Masahiro Yanagawa  8 , Yasushi Shintani  9 , Mari Nogami-Itoh  5 , Kenji Mizuguchi  5   10 , Jun Adachi  11 , Takeshi Tomonaga  11   12 , Yoshikazu Inoue  13   14 , Atsushi Kumanogoh  1   15   16   17   18

Affiliations

  • 1 Department of Respiratory Medicine and Clinical Immunology and.
  • 2 Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • 3 Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
  • 4 Department of Respiratory Medicine, Kinki Central Hospital of the Mutual Aid Association of Public School Teachers, Itami, Hyogo, Japan.
  • 5 Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and Nutrition, Settsu, Osaka, Japan.
  • 6 Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
  • 7 Department of Pathology.
  • 8 Department of Radiology, and.
  • 9 Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • 10 Laboratory for Computational Biology, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
  • 11 Laboratory of Proteomics for Drug Discovery, Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
  • 12 Proteobiologics Co., Ltd., Minoh, Osaka, Japan.
  • 13 Clinical Research Center, NHO Kinki Chuo Chest Medical Center, Sakai, Osaka, Japan.
  • 14 Osaka Anti-tuberculosis Association, Osaka Fukujuji Hospital, Neyagawa, Osaka, Japan.
  • 15 Center for Infectious Diseases for Education and Research (CiDER).
  • 16 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI).
  • 17 Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC); and.
  • 18 Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Osaka University, Suita, Osaka, Japan.

Free article

Abstract

Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.

Keywords: Fibrosis; Proteomics; Pulmonary surfactants; Pulmonology.

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