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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-02-22

AUTHORS

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

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. More... »

PAGES

581-590

Journal

TITLE

Cell Stress and Chaperones

ISSUE

5

VOLUME

18

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12192-013-0411-5

DOI

http://dx.doi.org/10.1007/s12192-013-0411-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022407849

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23435730


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27 schema:description 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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34 HSP47
35 HSP47 expression
36 HSP47 levels
37 Krebs von den Lungen-6
38 Lungen-6
39 S-IPF
40 accuracy
41 acute exacerbation
42 alveolar damage
43 analysis
44 autopsy tissue
45 biopsy
46 biosynthesis
47 chaperones
48 characteristic curve
49 collagen molecules
50 collagen production
51 collagen-specific molecular chaperone
52 conditions
53 curves
54 cutoff
55 damage
56 dehydrogenase
57 diagnostic accuracy
58 differences
59 diffuse alveolar damage
60 downregulation
61 exacerbation
62 expression
63 fibrogenic mechanisms
64 fibrosis
65 fibrosis model
66 fibrosis progression
67 heat shock protein 47
68 high diagnostic accuracy
69 idiopathic pulmonary fibrosis
70 immunohistochemical analysis
71 interstitial pneumonia
72 levels
73 mL
74 mechanism
75 model
76 molecular chaperones
77 molecules
78 pathogenic differences
79 pathophysiology
80 patients
81 pg/mL
82 pneumonia
83 previous studies
84 production
85 progression
86 protein
87 protein 47
88 pulmonary fibrosis
89 receiver
90 secretion
91 sensitivity
92 serum levels
93 shock protein 47
94 sp
95 specificity
96 study
97 subjects
98 surfactant proteins
99 tissue
100 usual interstitial pneumonia
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