Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis
Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis
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DOI：
10.1007/s12192-013-0411-5
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发表时间：
2013-09-01
影响因子：
3.8
通讯作者：
Kohno, Shigeru
中科院分区：
文献类型：
--
作者：
Kakugawa, Tomoyuki;Yokota, Shin-ichi;Kohno, Shigeru
特发性肺纤维化（IPF）急性加重（AE）的病理生理学知之甚少。热休克蛋白47（HSP 47）是一种胶原蛋白特异性分子伴侣，在胶原蛋白的合成和分泌过程中起重要作用。先前在实验动物纤维化模型中的研究表明，HSP 47表达的下调减少了胶原蛋白的产生并减少了纤维化进展。在本研究中，评价了血清HSP 47水平，以阐明AE-IPF和稳定型（S）-IPF之间涉及HSP 47的致病差异。受试者包括20例AE-IPF和33例S-IPF患者。检测血清HSP 47、KL-6、表面活性蛋白（SP）-A、SP-D和乳酸脱氢酶（LDH）水平。免疫组化法检测弥漫性肺泡损伤（DAD）和普通型间质性肺炎（UIP）活检和尸检肺组织中HSP 47的表达。AE-IPF患者的血清HSP 47水平显著高于S-IPF患者，而血清KL-6、SP-A和SP-D水平无显著差异。受试者工作特征曲线显示HSP 47在区分AE-IPF和S-IPF方面具有上级优势。HSP 47诊断准确性最高的临界值为559.4 pg/mL，敏感性、特异性和诊断准确性分别为100.0%、93.9%和96.2%。免疫组化结果显示DAD肺组织中HSP 47的表达高于UIP。AE-IPF患者的血清HSP 47显著高于S-IPF患者，表明两种疾病中涉及HSP 47的潜在纤维化机制不同。
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.