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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >The ErbB4 receptor in fetal rat lung fibroblasts and epithelial type II cells
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The ErbB4 receptor in fetal rat lung fibroblasts and epithelial type II cells

机译：胎鼠肺成纤维细胞和II型上皮细胞中的ErbB4受体

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摘要

ErbB receptors are important regulators of fetal organ development, including the fetal lung. They exhibit diversity in signaling potential, acting through homo- and heterodimers to cause different biological responses. We hypothesized that ErbB receptors show cell-specific and stimuli-specific activation, heterodimerization, and cellular localization patterns in fetal lung. We investigated this using immunoblotting, co-immunoprecipitation, and confocal microscopy in primary isolated E19 fetal rat lung fibroblasts and epithelial type II cells, stimulated with epidermal growth factor, transforming growth factor α, neuregulin 1β, or treated with conditioned medium (CM) from the respective other cell type. Fetal type II cells expressed significantly more ErbB1, ErbB2, and ErbB3 protein than fibroblasts. ErbB4 was consistently identified by co-immunoprecipitation of all other ErbB receptors in both cell types independent of the treatments. Downregulation of ErbB4 in fibroblasts initiated cell–cell communication that stimulated surfactant phospholipid synthesis in type II cells. Confocal microscopy in type II cells revealed nuclear localization of all receptors, most prominently for ErbB4. Neuregulin treatment resulted in relocation to the extra-nuclear cytoplasmic region, which was distinct from fibroblast CM treatment which led to nuclear localization of ErbB4 and ErbB2, inducing co-localization of both receptors. We speculate that ErbB4 plays a prominent role in fetal lung mesenchyme–epithelial communication.
机译：ErbB受体是胎儿器官发育的重要调节剂，包括胎儿肺。它们表现出信号传导潜能的多样性，通过同二聚体和异二聚体起作用，从而引起不同的生物学反应。我们假设ErbB受体在胎儿肺中显示细胞特异性和刺激特异性激活，异二聚化和细胞定位模式。我们使用免疫印迹，免疫共沉淀和共聚焦显微镜在经分离的E19胎鼠肺成纤维细胞和II型上皮细胞中进行了免疫印迹，共免疫显微镜研究，用表皮生长因子，转化生长因子α，神经调节蛋白1β刺激，或用来自相应的其他单元格类型。胎儿II型细胞表达的ErbB1，ErbB2和ErbB3蛋白明显多于成纤维细胞。通过与两种细胞类型无关的所有其他ErbB受体的共免疫沉淀作用，一致地鉴定了ErbB4。成纤维细胞中ErbB4的下调启动了细胞间的通讯，从而刺激了II型细胞中表面活性剂磷脂的合成。 II型细胞的共聚焦显微镜检查显示了所有受体的核定位，其中最明显的是ErbB4。神经调节蛋白的处理导致细胞外区域的重新定位，这与成纤维细胞CM处理不同，成纤维细胞CM处理导致ErbB4和ErbB2的核定位，并诱导了这两种受体的共定位。我们推测，ErbB4在胎儿肺间质与上皮的沟通中起着重要作用。

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