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Open Access 01-12-2014 | Research article

Serum heat shock protein 47 levels are elevated in acute interstitial pneumonia

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

Published in: BMC Pulmonary Medicine | Issue 1/2014

Abstract

Background

Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. We hypothesized that HSP47 could be a useful marker for fibrotic lung disease. The aim of this study was to evaluate serum levels of HSP47 in patients with various idiopathic interstitial pneumonias (IIPs).

Methods

Subjects comprised 9 patients with acute interstitial pneumonia (AIP), 12 with cryptogenic organizing pneumonia (COP), 16 with nonspecific interstitial pneumonia (NSIP), 19 with idiopathic pulmonary fibrosis (IPF), and 19 healthy adult volunteers.

Results

Patients with AIP had serum HSP47 levels that were significantly higher than those of COP, NSIP or IPF patients and those of healthy volunteers. In contrast, serum levels of HSP47 among patients with COP, NSIP, IPF, and healthy volunteers did not differ significantly. Receiver operating characteristic curves revealed that the cut-off level for HSP47 that resulted in the highest diagnostic accuracy for discriminating between AIP and COP, NSIP, IPF, and healthy controls was 859.3 pg/mL. The sensitivity, specificity, and diagnostic accuracy were 100.0%, 98.5%, and 98.7%, respectively.

Conclusion

The present results demonstrate that, among patients with various IIPs, serum levels of HSP47 were elevated specifically in patients with AIP.

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American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias: this joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002, 165 (2): 277-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11790668,

Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF: An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011, 183 (6): 788-824. 10.1164/rccm.2009-040GL.CrossRefPubMed

Hunninghake GW, Zimmerman MB, Schwartz DA, King TE, Lynch J, Hegele R, Waldron J, Colby T, Muller N, Lynch D, Galvin J, Gross B, Hogg J, Toews G, Helmers R, Cooper JA, Baughman R, Strange C, Millard M: Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001, 164 (2): 193-196. 10.1164/ajrccm.164.2.2101090.CrossRefPubMed

Stahel RA, Gilks WR, Lehmann HP, Schenker T: Third international workshop on lung tumor and differentiation antigens: overview of the results of the central data analysis. Int J Cancer Suppl. 1994, 8: 6-26.CrossRefPubMed

Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M: New serum indicator of interstitial pneumonitis activity: sialylated carbohydrate antigen KL-6. Chest. 1989, 96 (1): 68-73. 10.1378/chest.96.1.68.CrossRefPubMed

Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, Bando M, Sugiyama Y, Totani Y, Ishizaki T, Ichiyasu H, Suga M, Hamada H, Kohno N: Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology. 2006, 11 (2): 164-168. 10.1111/j.1440-1843.2006.00834.x.CrossRefPubMed

Greene KE, King TE, Kuroki Y, Bucher-Bartelson B, Hunninghake GW, Newman LS, Nagae H, Mason RJ: Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J. 2002, 19 (3): 439-446. 10.1183/09031936.02.00081102.CrossRefPubMed

Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y, Shiratori M, Kuroki Y, Abe S: Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med. 2000, 162 (3 Pt 1): 1109-1114.CrossRefPubMed

Kobayashi J, Kitamura S: KL-6: a serum marker for interstitial pneumonia. Chest. 1995, 108 (2): 311-315. 10.1378/chest.108.2.311.CrossRefPubMed

10.

Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N: Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med. 2002, 165 (3): 378-381. 10.1164/ajrccm.165.3.2107134.CrossRefPubMed

11.

Nakajima H, Harigai M, Hara M, Hakoda M, Tokuda H, Sakai F, Kamatani N, Kashiwazaki S: KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases. J Rheumatol. 2000, 27 (5): 1164-1170.PubMed

12.

Kinder BW, Brown KK, McCormack FX, Ix JH, Kervitsky A, Schwarz MI, King TE: Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest. 2009, 135 (6): 1557-1563. 10.1378/chest.08-2209.CrossRefPubMedPubMedCentral

13.

Al-Salmi QA, Walter JN, Colasurdo GN, Sockrider MM, Smith EO, Takahashi H, Fan LL: Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease. Chest. 2005, 127 (1): 403-407. 10.1378/chest.127.1.403.CrossRefPubMed

14.

Nagata K, Saga S, Yamada KM: A major collagen-binding protein of chick embryo fibroblasts is a novel heat shock protein. J Cell Biol. 1986, 103 (1): 223-229. 10.1083/jcb.103.1.223.CrossRefPubMed

15.

Nagai N, Hosokawa M, Itohara S, Adachi E, Matsushita T, Hosokawa N, Nagata K: Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis. J Cell Biol. 2000, 150 (6): 1499-1506. 10.1083/jcb.150.6.1499.CrossRefPubMedPubMedCentral

16.

Sauk JJ, Smith T, Norris K, Ferreira L: Hsp47 and the translation-translocation machinery cooperate in the production of alpha 1(I) chains of type I procollagen. J Biol Chem. 1994, 269 (6): 3941-3946.PubMed

17.

Taguchi T, Razzaque MS: The collagen-specific molecular chaperone HSP47: is there a role in fibrosis?. Trends Mol Med. 2007, 13 (2): 45-53. 10.1016/j.molmed.2006.12.001.CrossRefPubMed

18.

Razzaque MS, Hossain MA, Kohno S, Taguchi T: Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47. Virchows Arch. 1998, 432 (5): 455-460. 10.1007/s004280050191.CrossRefPubMed

19.

Ishii H, Mukae H, Kakugawa T, Iwashita T, Kaida H, Fujii T, Hayashi T, Kadota J, Kohno S: Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy. Am J Physiol Lung Cell Mol Physiol. 2003, 285 (4): L957-L963.CrossRefPubMed

20.

Kakugawa T, Mukae H, Hishikawa Y, Ishii H, Sakamoto N, Ishimatsu Y, Fujii T, Koji T, Kohno S: Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis. Virchows Arch. 2010, 456 (3): 309-315. 10.1007/s00428-009-0876-x.CrossRefPubMed

21.

Razzaque MS, Nazneen A, Taguchi T: Immunolocalization of collagen and collagen-binding heat shock protein 47 in fibrotic lung diseases. Mod Pathol. 1998, 11 (12): 1183-1188.PubMed

22.

Kakugawa T, Mukae H, Hayashi T, Ishii H, Nakayama S, Sakamoto N, Yoshioka S, Sugiyama K, Mine M, Mizuta Y, Kohno S: Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial pneumonia. Respir Res. 2005, 6: 57-10.1186/1465-9921-6-57.CrossRefPubMedPubMedCentral

23.

Kakugawa T, Yokota S, Ishimatsu Y, Hayashi T, Nakashima S, Hara S, Sakamoto N, Kubota H, Mine M, Matsuoka Y, Mukae H, Nagata K, Kohno S: Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis. Cell Stress Chaperones. 2013, 18 (5): 581-590. 10.1007/s12192-013-0411-5.CrossRefPubMedPubMedCentral

24.

Razzaque MS, Foster CS, Ahmed AR: Role of collagen-binding heat shock protein 47 and transforming growth factor-beta1 in conjunctival scarring in ocular cicatricial pemphigoid. Invest Ophthalmol Vis Sci. 2003, 44 (4): 1616-1621. 10.1167/iovs.02-0644.CrossRefPubMed

25.

Razzaque MS, Kumatori A, Harada T, Taguchi T: Coexpression of collagens and collagen-binding heat shock protein 47 in human diabetic nephropathy and IgA nephropathy. Nephron. 1998, 80 (4): 434-443. 10.1159/000045217.CrossRefPubMed

26.

Brown KE, Broadhurst KA, Mathahs MM, Brunt EM, Schmidt WN: Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver. Lab Invest. 2005, 85 (6): 789-797. 10.1038/labinvest.3700271.CrossRefPubMed

27.

Amenomori M, Mukae H, Sakamoto N, Kakugawa T, Hayashi T, Hara A, Hara S, Fujita H, Ishimoto H, Ishimatsu Y, Nagayasu T, Kohno S: HSP47 in lung fibroblasts is a predictor of survival in fibrotic nonspecific interstitial pneumonia. Respir Med. 2010, 104 (6): 895-901. 10.1016/j.rmed.2010.01.011.CrossRefPubMed

28.

Yokota S, Kubota H, Matsuoka Y, Naitoh M, Hirata D, Minota S, Takahashi H, Fujii N, Nagata K: Prevalence of HSP47 antigen and autoantibodies to HSP47 in the sera of patients with mixed connective tissue disease. Biochem Biophys Res Commun. 2003, 303 (2): 413-418. 10.1016/S0006-291X(03)00352-8.CrossRefPubMed

29.

Collard HR, Calfee CS, Wolters PJ, Song JW, Hong SB, Brady S, Ishizaka A, Jones KD, King TE, Matthay MA, Kim DS: Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2010, 299 (1): L3-L7. 10.1152/ajplung.90637.2008.CrossRefPubMedPubMedCentral

30.

Iwashita T, Kadota J, Naito S, Kaida H, Ishimatsu Y, Miyazaki M, Ozono Y, Kohno S: Involvement of collagen-binding heat shock protein 47 and procollagen type I synthesis in idiopathic pulmonary fibrosis: contribution of type II pneumocytes to fibrosis. Hum Pathol. 2000, 31 (12): 1498-1505. 10.1053/hupa.2000.20378.CrossRefPubMed

31.

Kakugawa T, Mukae H, Hayashi T, Ishii H, Abe K, Fujii T, Oku H, Miyazaki M, Kadota J, Kohno S: Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis. Eur Respir J. 2004, 24 (1): 57-65. 10.1183/09031936.04.00120803.CrossRefPubMed

32.

Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med. 2000, 342 (18): 1334-1349. 10.1056/NEJM200005043421806.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/14/48/prepub

Title: Serum heat shock protein 47 levels are elevated in acute interstitial pneumonia
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
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Pulmonary Medicine / Issue 1/2014
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/1471-2466-14-48

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Serum heat shock protein 47 levels are elevated in acute interstitial pneumonia

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Conclusion

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