Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Virchows Arch. 2010 Mar;456(3):309-15. doi: 10.1007/s00428-009-0876-x. Epub 2010 Jan 22.
Heat shock protein 47 (HSP47) 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 per day of bleomycin for five 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 alpha-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.
热休克蛋白 47(HSP47)是一种胶原特异性分子伴侣,它在原胶原的加工和/或分泌中起着重要作用。然而,关于肺纤维化中哪些细胞实际上在合成 HSP47 仅限于知识层面。本研究旨在通过原位杂交技术研究 HSP47 信使核糖核酸(mRNA)在正常肺和博莱霉素诱导的肺纤维化小鼠肺中的定位。为此,将 ICR 小鼠连续 5 天每天静脉注射 10mg/kg 博莱霉素。通过原位杂交技术,在对照组(仅生理盐水)和博莱霉素处理组的小鼠中鉴定出表达 HSP47 mRNA 的肺细胞。与对照组相比,博莱霉素处理的肺中 HSP47 mRNA 的信号明显增加。HSP47 mRNA 定位于活性纤维化区域中的α-平滑肌肌动蛋白阳性肌成纤维细胞、表面活性蛋白-A 阳性 II 型肺泡细胞和 F4/80 阳性巨噬细胞中。这些结果表明,这些细胞可能通过上调 HSP47 mRNA 在博莱霉素处理的肺纤维化过程中合成原胶原,并在纤维化发生中发挥重要作用。