Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

Kakugawa, Tomoyuki; Mukae, Hiroshi; Hayashi, Tomayoshi; Ishii, Hiroshi; Nakayama, Seiko; Sakamoto, Noriho; Yoshioka, Sumako; Sugiyama, Kanako; Mine, Mariko; Mizuta, Yohei; Kohno, Shigeru

doi:10.1186/1465-9921-6-57

Cited by 46 publications

(52 citation statements)

References 31 publications

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“…We also previously reported that regenerated type II pneumocytes in usual interstitial pneumonia express HSP47 [17,18]. These findings suggest that type II pneumocytes in addition to myofibroblasts become synthesizing procollagen through the induction of HSP47 and play an important role in the development of fibrosis.…”

Section: Introductionsupporting

confidence: 56%

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Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis

et al. 2010

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Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that has been shown to play a major role in the processing and/or secretion of procollagen. However, the knowledge on which cells are actually synthesizing HSP47 in the lung parenchyma in pulmonary fibrosis was only limited. The aim of the present study was to investigate the localization of HSP47 messenger ribonucleic acid (mRNA) in normal lung, and in the lungs of mice in bleomycin-induced pulmonary fibrosis, using in situ hybridization.For the purpose, ICR mice were intravenously injected with 10 mg/kg/day of bleomycin for 5 consecutive days. The lung cells expressing HSP47 mRNA were identified in control (saline alone) and bleomycin-treated mice by in situ hybridization. The signal for HSP47 mRNA was markedly increased in bleomycin-treated lungs compared with that of controls. HSP47 mRNA was localized in -smooth muscle actin-positive myofibroblasts, surfactant protein A-positive type II pneumocytes and F4/80 positive macrophages in the active fibrotic areas. These results suggest that these cells may synthesize procollagen in the fibrotic process of bleomycin-treated lungs through upregulation of HSP47 mRNA and play an important role in fibrogenesis.

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Section: Introductionsupporting

confidence: 56%

“…In addition, we previously reported that the expression of human HSP47 was increased in the fibrotic lesions of idiopathic pulmonary fibrosis (IPF) [17,18], fibrotic transplanted kidney [19], and peritoneal sclerosis [20]. These findings suggest HSP47 may play the important role in collagen synthesis in various fibrotic disorders.…”

Section: Introductionmentioning

confidence: 94%

Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis

et al. 2010

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“…Other studies have demonstrated that HSP47 expression is highly tissue-and cell-specific, mainly restricted to phenotypically altered collagen producing cells and is well correlated with expression of collagen (Ishii et al 2003;Iwashita et al 2000;Kakugawa et al 2004Kakugawa et al , 2005Kakugawa et al , 2010Abe et al 2000;Shioshita et al 2000). It was reported that HSP47 expression was higher in the lungs of patients with idiopathic usual interstitial pneumonia (UIP) than in those with collagen vascular disease-associated UIP and idiopathic nonspecific interstitial pneumonia (NSIP) (Kakugawa et al 2005); idiopathic fibrotic NSIP patients with higher pulmonary HSP47 expression had poorer prognosis than patients with lower levels (Amenomori et al 2010). These findings suggest that HSP47 plays an important role in the fibrotic process and correlates with fibrotic disease activity.…”

Section: Introductionmentioning

confidence: 99%

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

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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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. -013-0411-5 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.Cell Stress and Chaperones (2013) 18:581-590 DOI 10.1007/s12192

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“…Research into the pathogenesis of IPF has advanced considerably in recent years and has shifted its focus from processes governing chronic inflammation with fibrosis as end result, to alveolar epithelial dysfunction and injury with aberrant wound repair and disordered fibroproliferation [14][15]. A range of molecules involved in epithelial damage and repair (eg surfactant-protein (SP)-A, and SP-D, Krebs von den Lungen (KL)-6, Clara cell secretory protein (CC)-16), inflammation (CD28, MCP-1, MIP1a, CXCL-11, TNF, LDH, sIL-2R, CCL-18), myofibroblast accumulation and matrix deposition (circulating fibrocytes, Heat shock protein 47 (HSP47), matrix metalloproteinases (MMPs), TGFβ), angiogenesis (vascular endothelial growth factor (VEGF), IL-8), coagulation and oxidative stress [16], have been described as potential serum, BAL and tissue biomarkers [17][18][19][20]. Biomarkers should ideally be easily obtained in a non-invasive manner and validated for use in every day practice.…”

Section: Candidate Biomarkersmentioning

confidence: 99%