Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis
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- 作者：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) - 关键词：Acute exacerbation of idiopathic pulmonary fibrosis ; Heat shock protein 47 ; Krebs von den Lungen ; 6 ; Surfactant protein A ; Surfactant protein D
- 刊名：Cell Stress and Chaperones
- 出版年：2013
- 出版时间：September 2013
- 年：2013
- 卷：18
- 期：5
- 页码：581-590
- 全文大小：501KB
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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. Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
2. Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan
3. Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan
4. Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
5. Department of Life Science, Faculty and Graduate School of Engineering and Resource Science, Akita University, Akita, Japan
6. Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
7. Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
8. Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan - ISSN：1466-1268
文摘
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.