Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury
Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury
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DOI：
10.1152/ajplung.2001.280.4.l695
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发表时间：
2001-04-01
影响因子：
4.9
通讯作者：
Costa, RH
中科院分区：
文献类型：
--
作者：
Kalinichenko, VV;Lim, L;Costa, RH
叉头盒蛋白（Fox）是一个不断发展的转录因子家族，在细胞增殖和分化以及器官形态发生中起重要作用。Fox家族成员肝细胞核因子(HNF)-3 β (Foxa2)和HNF-3/叉头同源物(HFH)-8 （FREAC-1, Foxf1）分别在成人肺上皮细胞和间充质细胞中表达，但这些细胞仅表达低水平的增殖特异性hhh - 11b基因（Trident, Foxm1b）。然而，这些Fox转录因子在急性肺损伤反应中的调节作用尚未确定。我们在此报道了使用丁基羟基甲苯（BHT）介导的肺损伤，以证明hhh -11蛋白和RNA水平在肺修复期间显着增加。hhh -11在BHT损伤后第2天达到最高水平，此时细支气管和肺泡上皮细胞均发生广泛增殖。虽然BHT肺损伤没有改变上皮细胞HNF-3 β的表达，但在间充质细胞增殖期间观察到hhf -8 mRNA水平降低65%。表达hhh -8的细胞与血小板内皮细胞、粘附分子1阳性的肺泡内皮细胞和α -平滑肌肌动蛋白阳性的细支气管周围平滑肌细胞共定位。
The forkhead box (Fox) proteins are a growing family of transcription factors that have important roles in cellular proliferation and differentiation and in organ morphogenesis. The Fox family members hepatocyte nuclear factor (HNF)-3 beta (Foxa2) and HNF-3/forkhead homolog (HFH)-8 (FREAC-1, Foxf1) are expressed in adult pulmonary epithelial and mesenchymal cells, respectively, but these cells display only low expression levels of the proliferation-specific HFH-11B gene (Trident, Foxm1b). The regulation of these Fox transcription factors in response to acute lung injury, however, has yet to be determined. We report here on the use of butylated hydroxytoluene (BHT)-mediated lung injury to demonstrate that HFH-11 protein and RNA levels were markedly increased throughout the period of lung repair. The maximum levels of HFH-11 were observed by day 2 following BHT injury when both bronchiolar and alveolar epithelial cells were undergoing extensive proliferation. Although BHT lung injury did not alter epithelial cell expression of HNF-3 beta, a 65% reduction in HFH-8 mRNA levels was observed during the period of mesenchymal cell proliferation. HFH-8-expressing cells were colocalized with platelet endothelial cell adhesion molecule-1-positive alveolar endothelial cells and with alpha -smooth muscle actin-positive peribronchiolar smooth muscle cells.