Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis
Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis
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DOI：
10.1007/s00428-009-0876-x
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发表时间：
2010-03-01
期刊：
影响因子：
3.5
通讯作者：
Kohno, Shigeru
中科院分区：
文献类型：
--
作者：
Kakugawa, Tomoyuki;Mukae, Hiroshi;Kohno, Shigeru
热休克蛋白47（HSP 47）是一种胶原特异性分子伴侣，已被证明在前胶原的加工和/或分泌中起主要作用。然而，关于肺纤维化中肺实质中哪些细胞实际上合成HSP 47的知识有限。采用原位杂交技术研究了热休克蛋白47（HSP 47）mRNA在正常肺组织和博莱霉素诱导的肺纤维化小鼠肺组织中的定位。为此，ICR小鼠静脉注射10 mg/kg/天的博来霉素，连续5天。通过原位杂交，在对照组（仅生理盐水）和博来霉素处理的小鼠中鉴定表达HSP 47 mRNA的肺细胞。与对照组相比，博来霉素处理的肺中HSP 47 mRNA的信号显著增加。HSP 47 mRNA定位于α-平滑肌肌动蛋白阳性的肌成纤维细胞，表面活性蛋白A阳性的II型肺细胞，和F4/80阳性的巨噬细胞在活动性纤维化地区。这些结果表明，这些细胞可能合成前胶原在博莱霉素治疗肺纤维化过程中通过上调HSP 47 mRNA，并在纤维化中发挥重要作用。
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.