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Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

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Cell Stress and Chaperones Aims and scope

Abstract

Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic differences involving HSP47 between AE-IPF and stable (S)-IPF. Subjects comprised 20 AE-IPF and 33 S-IPF patients. Serum levels of HSP47, Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-A, SP-D, and lactate dehydrogenase (LDH) were measured. Immunohistochemical analysis of lung HSP47 expression was determined in biopsy and autopsy tissues diagnosed as diffuse alveolar damage (DAD) and usual interstitial pneumonia (UIP). Serum levels of HSP47 were significantly higher in AE-IPF than in S-IPF patients, whereas serum levels of KL-6, SP-A, and SP-D did not differ significantly. Receiver operating characteristic curves revealed that HSP47 was superior for discriminating AE-IPF and S-IPF. The cutoff for HSP47 resulting in the highest diagnostic accuracy was 559.4 pg/mL; sensitivity, specificity, and diagnostic accuracy were 100.0 %, 93.9 %, and 96.2 %, respectively. Immunohistochemical analysis revealed that pulmonary HSP47 expression was greater in DAD than UIP tissues. Serum HSP47 was significantly higher in AE-IPF than in S-IPF patients, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions.

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Acknowledgments

The authors thank Dr. M. Kitaichi (Department of Laboratory Medicine and Pathology, NHO Kinki-chuo Chest Medical Center, Sakai, Japan) for the valuable advice regarding pathological diagnosis; Prof. T. Nagayasu (Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan) for performing the surgical lung biopsies and providing the tissues that made this work possible; and Mr. A. Yokoyama for the excellent technical support.

This study was supported in part by a research grant from Takeda Science Foundation and The Kato Memorial Trust for Nambyo Research. This study was also partly supported by a grant to the Diffuse Lung Diseases Research Group from the Ministry of Health, Labour and Welfare, in Japan.

Competing interests

T. Kakugawa received a research grant from Takeda Science Foundation and the Kato Memorial Trust for Nambyo Research. T. Kakugawa and S. Yokota have a patent application pending for research related to this manuscript. Y. Ishimatsu and N. Sakamoto received a research grant from the Ministry of Education, Science, Sports, and Culture of Japan.

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Authors and Affiliations

  1. Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Tomoyuki Kakugawa, Yuji Ishimatsu, Shota Nakashima, Shintaro Hara, Noriho Sakamoto & Shigeru Kohno

  2. Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Shin-ichi Yokota

  3. Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan

    Tomayoshi Hayashi

  4. Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

    Hiroshi Kubota, Yasuhiro Matsuoka & Kazuhiro Nagata

  5. Department of Life Science, Faculty and Graduate School of Engineering and Resource Science, Akita University, Akita, Japan

    Hiroshi Kubota

  6. Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Mariko Mine

  7. Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Hiroshi Mukae

  8. Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan

    Kazuhiro Nagata

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  1. Tomoyuki Kakugawa
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  2. Shin-ichi Yokota
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  3. Yuji Ishimatsu
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  4. Tomayoshi Hayashi
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  11. Hiroshi Mukae
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Correspondence to Tomoyuki Kakugawa.

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Kakugawa, T., Yokota, Si., Ishimatsu, Y. et al. Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis. Cell Stress and Chaperones 18, 581–590 (2013). https://doi.org/10.1007/s12192-013-0411-5

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  • DOI: https://doi.org/10.1007/s12192-013-0411-5

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