Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis

Kakugawa, Tomoyuki; Mukae, Hiroshi; Hishikawa, Yoshitaka; Ishii, Hiroshi; Sakamoto, Noriho; Ishimatsu, Yuji; Fujii, Takeshi; Koji, Takehiko; Kohno, Shigeru

doi:10.1007/s00428-009-0876-x

Cited by 24 publications

(17 citation statements)

References 34 publications

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“…Hence, the increase of HSP47 might be a specific reflection of pulmonary fibrotic activity in patients with DILD. Irrespective of the primary disease, upregulation of HSP47 is a common phenomenon during the fibrotic process of any organ [8-15,17-19]. Therefore, it is likely that assessment of serum HSP47 levels might help to define those patients at risk of developing fibrotic complications and to monitor the response to treatment.…”

Section: Discussionmentioning

confidence: 99%

Serum heat shock protein 47 levels in patients with drug-induced lung disease

Kakugawa¹,

Yokota²,

Ishimatsu³

et al. 2013

Respir Res

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BackgroundHeat shock protein (HSP) 47 is a collagen-specific molecular chaperone that is required for molecular maturation of various types of collagens. We recently reported that HSP47 serum levels were markedly higher in patients with acute exacerbations of idiopathic pulmonary fibrosis (IPF) when compared with patients with stable IPF, suggesting that serum HSP47 levels correlate with interstitial pneumonia activity. The aim of this study was to evaluate serum HSP47 levels in patients with drug-induced lung disease (DILD).MethodsFindings from high-resolution computed tomographic chest scans of 47 patients with DILD were classified into one of four predominant patterns: organizing pneumonia (OP) (n = 4), nonspecific interstitial pneumonia (NSIP) (n = 24), hypersensitivity pneumonitis (HP) (n = 11), and diffuse alveolar damage (DAD) (n = 8). Serum levels of HSP47, Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-A, and SP-D were measured in these patients.ResultsThe PaO2/fraction of inspired oxygen (FiO2) (P/F) ratios were significantly lower and the alveolar-arterial difference of oxygen (A-a DO2) was significantly higher in the DAD group than in the other groups. Patients with DAD had the worst outcomes among the different subgroups. Patients in the DAD group had significantly higher serum HSP47 levels than those in other groups. Receiver operating characteristic curves revealed that HSP47 was superior to KL-6, SP-A, and SP-D for discriminating between the DAD group and the other groups. The cut-off level for HSP47 that resulted in the highest diagnostic accuracy was 1711.5 pg/mL. The sensitivity, specificity, and diagnostic accuracy were 87.5%, 97.4%, and 95.7%, respectively. Serum levels of HSP47 in the group of patients requiring glucocorticoids were significantly higher than those in patients who experienced clinical improvement without glucocorticoid administration. Serum HSP47 levels also significantly correlated with various respiratory parameters.ConclusionThis study demonstrated that serum HSP47 levels were elevated in patients with DILD with a DAD pattern who had the worst outcomes among the different subgroups, and that this was correlated with P/F ratio and A-a DO2.

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Section: Discussionmentioning

confidence: 99%

Serum heat shock protein 47 levels in patients with drug-induced lung disease

Kakugawa¹,

Yokota²,

Ishimatsu³

et al. 2013

Respir Res

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“…α-SMA, a downstream molecule of TGF-β1, is known to be critical for pulmonary fibrosis (5,6). HSP47 mRNA was found to be localized in α-SMA-positive myofibroblasts in the active fibrotic areas (23), however, the precise association between HSP47 and α-SMA remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Anti-profibrotic effects of artesunate on bleomycin-induced pulmonary fibrosis in Sprague Dawley rats

Wang

Xuan

Yao

et al. 2012

Molecular Medicine Reports

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The present study aimed to determine whether artesunate has beneficial effects on bleomycin-induced pulmonary fibrosis in rats and to examine the possible mechanisms underlying these effects. All experiments were performed with male Sprague Dawley rats weighing 180-250 g. Animals were randomly divided into four experimental groups that were administered either saline alone, artesunate alone, bleomycin alone or bleomycin + artesunate. Lung histopathology was investigated by hematoxylin and eosin staining and Masson staining. Lung profibrotic molecules were analyzed by reverse transcription polymerase chain reaction, immunoblotting and immunohistochemistry. In rats treated with artesunate, pulmonary fibrosis induced by bleomycin was significantly reduced. Administration of artesunate significantly improved bleomycin-induced morphological alterations. Profibrotic molecules, including transforming growth factor-β1, Smad3, heat shock protein 47, α-smooth muscle actin and collagen type I were also reduced by artesunate. These findings suggest that artesunate improves bleomycin-induced pulmonary fibrosis pathology in rats possibly by inhibiting profibrotic molecules associated with pulmonary fibrosis.

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“…Recent studies have demonstrated that HSP47 expression is highly tissue-and cell-specific—mainly restricted to phenotypically altered collagen-producing cells [17]. HSP47 expression is upregulated in animals with experimentally induced pulmonary fibrosis [18-20]. Previous studies have also shown that expression of human HSP47 is increased in fibrotic lesions of idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (NSIP), and diffuse alveolar damage (DAD) [21-23].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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BackgroundHeat 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).MethodsSubjects 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.ResultsPatients 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.ConclusionThe present results demonstrate that, among patients with various IIPs, serum levels of HSP47 were elevated specifically in patients with AIP.

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Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis

Cited by 24 publications

References 34 publications

Serum heat shock protein 47 levels in patients with drug-induced lung disease

Serum heat shock protein 47 levels in patients with drug-induced lung disease

Anti-profibrotic effects of artesunate on bleomycin-induced pulmonary fibrosis in Sprague Dawley rats

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

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