Bleomycin induces strain-dependent alterations in the pattern of epithelial cell-specific marker expression in mouse lung
Bleomycin induces strain-dependent alterations in the pattern of epithelial cell-specific marker expression in mouse lung
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DOI：
10.1006/taap.1996.8056
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发表时间：
1997-02-01
影响因子：
3.8
通讯作者：
Finkelstein, JN
中科院分区：
文献类型：
--
作者：
Daly, HE;BaecherAllan, CM;Finkelstein, JN
由于肺部毒性，抗肿瘤药物博莱霉素的临床应用受到限制。已经建立了博莱霉素诱导的小鼠肺纤维化模型，试图了解纤维化过程中涉及的机制。研究表明，博莱霉素治疗后肺泡上皮损伤较早。这项研究的目的是评估博莱霉素暴露后对博莱霉素诱导的纤维化易感性不同的小鼠呼吸道和肺泡上皮细胞中基因表达的模式。肺表面活性蛋白C(SPC)和Clara细胞特异性蛋白(CC10)分别作为肺泡II型细胞和呼吸道Clara细胞的细胞特异性标志物。小鼠气管内单次注射博莱霉素，通过原位杂交检测SPC和CC10转录本的模式。治疗28天后，对照组和耐药小鼠的SPC mRNA的表达模式是一致的，而在敏感小鼠则呈现出斑片状的外观。博莱霉素处理还导致cc10mRNA表达细胞的菌株依赖性丢失。在治疗后28天的敏感小鼠中，SPC mRNA在远端细支气管上皮中以一种形态上不同的细胞类型异位表达。连续切片显示，这些细胞或共表达CC10mRNA，或与含有CC10mRNA的细胞相邻。这种独特的细胞群可能代表了一种在上皮修复中重要的祖细胞类型。博莱霉素治疗后CC10和SPC基因表达的应变依赖性变化提示上皮细胞在肺纤维化与修复中发挥作用。(C)1997年学术出版社。
Clinical use of the antineoplastic agent bleomycin is restricted due to pulmonary toxicity. Murine models of bleomycin-induced pulmonary fibrosis have been developed in an attempt to understand the mechanisms involved in the fibrotic process. Studies have shown that the alveolar epithelium is damaged early after bleomycin treatment. The purpose of this study was to evaluate the pattern of gene expression in airway and alveolar epithelial cells after bleomycin exposure in mice that vary in susceptibility to bleomycin-induced fibrosis. Surfactant protein C (SPC) and Clara cell-specific protein (CC10) mRNA were used as cell-specific markers of alveolar type II cells and airway Clara cells, respectively. Mice were treated with a single intratracheal dose of bleomycin and the pattern of SPC and CC10 transcripts was examined by in situ hybridization. The pattern of SPC mRNA 28 days after treatment was uniform in controls and resistant mice but exhibited a patchy appearance in sensitive mice. Bleomycin treatment also resulted in a strain-dependent loss of CC10 mRNA-expressing cells. In sensitive mice 28 days after treatment, SPC mRNA was ectopically expressed in the distal bronchiolar epithelium in a morphologically distinct cell type. Serial sections revealed that these cells either coexpressed CC10 mRNA or were located adjacent to CC10 mRNA-containing cells. This unique cell population may represent a progenitor cell type important in epithelial repair. The strain-dependent changes in CC10 and SPC gene expression after bleomycin treatment are suggestive of a role for the epithelium in pulmonary fibrosis versus repair. (C) 1997 Academic Press.