Cell Stress and Chaperones

, Volume 18, Issue 5, pp 581–590 | Cite as

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

  • Tomoyuki Kakugawa
  • Shin-ichi Yokota
  • Yuji Ishimatsu
  • Tomayoshi Hayashi
  • Shota Nakashima
  • Shintaro Hara
  • Noriho Sakamoto
  • Hiroshi Kubota
  • Mariko Mine
  • Yasuhiro Matsuoka
  • Hiroshi Mukae
  • Kazuhiro Nagata
  • Shigeru Kohno
Original Paper

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.

Keywords

Acute exacerbation of idiopathic pulmonary fibrosis Heat shock protein 47 Krebs von den Lungen-6 Surfactant protein A Surfactant protein D 

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Copyright information

© Cell Stress Society International 2013

Authors and Affiliations

  • Tomoyuki Kakugawa
    • 1
  • Shin-ichi Yokota
    • 2
  • Yuji Ishimatsu
    • 1
  • Tomayoshi Hayashi
    • 3
  • Shota Nakashima
    • 1
  • Shintaro Hara
    • 1
  • Noriho Sakamoto
    • 1
  • Hiroshi Kubota
    • 4
    • 5
  • Mariko Mine
    • 6
  • Yasuhiro Matsuoka
    • 4
  • Hiroshi Mukae
    • 7
  • Kazuhiro Nagata
    • 4
    • 8
  • Shigeru Kohno
    • 1
  1. 1.Second Department of Internal MedicineNagasaki University School of MedicineNagasakiJapan
  2. 2.Department of MicrobiologySapporo Medical University School of MedicineSapporoJapan
  3. 3.Department of PathologyNagasaki University HospitalNagasakiJapan
  4. 4.Department of Molecular and Cellular Biology, Institute for Frontier Medical SciencesKyoto UniversityKyotoJapan
  5. 5.Department of Life Science, Faculty and Graduate School of Engineering and Resource ScienceAkita UniversityAkitaJapan
  6. 6.Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  7. 7.Department of Respiratory Medicine, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan
  8. 8.Laboratory of Molecular and Cellular Biology, Faculty of Life SciencesKyoto Sangyo UniversityKyotoJapan

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