Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study.
Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study.
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发表时间：
1994-07
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通讯作者：
Kai Zhang;M. Rekhter;D. Gordon;S. Phan
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作者：
Kai Zhang;M. Rekhter;D. Gordon;S. Phan
肺纤维化病变的一个特征是出现可收缩的负载有毒性物质的基质细胞或肌成纤维细胞。这些细胞在纤维化中的作用及其细胞骨架表型尚未完全阐明。本研究采用肺纤维化模型进一步研究这些问题。在第0天气管内用博莱霉素处理大鼠，通过原位杂交检测α 1（I）前胶原mRNA的表达，并通过免疫组织化学检测结蛋白和α-平滑肌肌动蛋白的表达，在不同的时间点检查大鼠的肺。结果显示，在用博来霉素处理的动物的肺中，类似成纤维细胞的细胞数量增加，并且α-平滑肌肌动蛋白、结蛋白和前胶原mRNA表达呈强阳性，其中在博来霉素处理后第7天至第14天之间增加最大。两种类型的新的阳性细胞可以辨别。第一个表达α-平滑肌肌动蛋白，结蛋白和前胶原mRNA定位于活动性纤维化病变。第二只表达α-平滑肌肌动蛋白和前胶原mRNA定位于纤维化亚mesotherapy地区。几乎所有的新反应性α-平滑肌肌动蛋白阳性细胞强烈表达前胶原mRNA，它们构成了大多数积极表达前胶原的细胞。这些发现表明，新出现的肌成纤维细胞的特点是α-平滑肌肌动蛋白和/或结蛋白表达可能是负责大多数，如果不是所有的肺胶原蛋白基因表达增加肺纤维化。
Appearance of contractile filament-laden stromal cells or myofibroblasts is a characteristic of lung fibrotic lesions. The role of these cells in fibrosis and their cytoskeletal phenotype are not fully delineated. This study was undertaken to further investigate these issues using a model of lung fibrosis. Rats were treated endotracheally with bleomycin on day 0, and their lungs examined at various time points by in situ hybridization for alpha 1(I) procollagen mRNA expression and by immunohistochemistry for desmin and alpha-smooth muscle actin expression. The results show an increase in the number of cells resembling fibroblasts and strongly positive for alpha-smooth muscle actin, desmin and procollagen mRNA expression in lungs of animals treated with bleomycin, with the increase being maximal between days 7 and 14 after bleomycin treatment. Two types of newly positive cells could be discerned. The first expressing alpha-smooth muscle actin, desmin, and procollagen mRNA was localized in active fibrotic lesions. The second expressing only alpha-smooth muscle actin and procollagen mRNA was localized in fibrotic submesothelial areas. Almost all of the newly reactive alpha-smooth muscle actin-positive cells strongly express procollagen mRNA, and they constituted most of the cells actively expressing procollagen. These findings suggest that the newly appearing myofibroblast characterized by alpha-smooth muscle actin and/or desmin expression may be responsible for most if not all of the increased lung collagen gene expression in pulmonary fibrosis.