Divergent gene regulation and growth effects by NF-κB in epithelial and mesenchymal cells of human skin
Divergent gene regulation and growth effects by NF-κB in epithelial and mesenchymal cells of human skin
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DOI：
10.1038/sj.onc.1206198
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发表时间：
2003-04-03
期刊：
影响因子：
8
通讯作者：
Khavari, PA
中科院分区：
文献类型：
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作者：
Hinata, K;Gervin, AM;Khavari, PA
NF-κ B以组织环境依赖性方式调节正常和病理过程，包括肿瘤形成。在皮肤中，NF-κ B参与表皮稳态以及鳞状细胞癌的发病机制;然而，其在底层间充质真皮中的功能尚不清楚。为了深入了解NF-kappaB在这两个相邻的皮肤组织区室中的作用，在表皮角质形成细胞和真皮成纤维细胞中确定了NF-kappaB对12435个基因表达的影响。虽然NF-κ B诱导的促炎和抗凋亡基因在这两种情况下，它表现出不同的生长调节基因的影响。在角质形成细胞中，而不是在成纤维细胞中，NF-κ B诱导p21（CIP 1），这足以抑制两种细胞类型的生长。相比之下，在两种情况下，NF-κ B均增加了生长抑制因子（GIF）的水平，但仅在角质形成细胞中抑制生长。这些发现表明，转录因子如NF-κ B可以通过差异靶基因诱导以及通过诱导共同靶点来编程组织选择性效应，所述共同靶点根据细胞谱系发挥不同的作用。
NF-kappaB regulates normal and pathological processes, including neoplasia, in a tissue-context-dependent manner. In skin, NF-kappaB is implicated in epidermal homeostasis as well as in the pathogenesis of squamous cell carcinoma; however, its function in the underlying mesenchymal dermis has been unclear. To gain insight into NF-kappaB roles in these two adjacent cutaneous tissue compartments, NF-kappaB effects on expression of 12 435 genes were determined in epidermal keratinocytes and dermal fibroblasts. Although NF-kappaB induced proinflammatory and antiapoptotic genes in both settings, it exhibited divergent effects on growth regulatory genes. In keratinocytes, but not in fibroblasts, NF-kappaB induced p21(CIP1), which was sufficient to inhibit growth of both cell types. Levels of growth inhibitory factor (GIF), in contrast, were increased by NF-kappaB in both settings but inhibited growth only in keratinocytes. These findings indicate that transcription factors such as NF-kappaB can program tissue-selective effects via both differential target gene induction as well as by inducing common targets that exert differing effects depending on cellular lineage.