title: Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis.
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.
authors: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. kakugawa@nagasaki-u.ac.jp
authors: Tomoyuki
authors: T
authors: Kakugawa
authors: Shin-Ichi
authors: S
authors: Yokota
authors: Yuji
authors: Y
authors: Ishimatsu
authors: Tomayoshi
authors: T
authors: Hayashi
authors: Shota
authors: S
authors: Nakashima
authors: Shintaro
authors: S
authors: Hara
authors: Noriho
authors: N
authors: Sakamoto
authors: Hiroshi
authors: H
authors: Kubota
authors: Mariko
authors: M
authors: Mine
authors: Yasuhiro
authors: Y
authors: Matsuoka
authors: Hiroshi
authors: H
authors: Mukae
authors: Kazuhiro
authors: K
authors: Nagata
authors: Shigeru
authors: S
authors: Kohno
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D050958:HSP47 Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D050958:HSP47 Heat-Shock Proteins; C060192:MUC1 protein, human; D018396:Mucin-1; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D007770:L-Lactate Dehydrogenase