Maytin E V, Habener J F
Department of Dermatology, Massachusetts General Hospital, Boston 02114, USA.
J Invest Dermatol. 1998 Mar;110(3):238-46. doi: 10.1046/j.1523-1747.1998.00123.x.
CCAAT-enhancer binding proteins (C/EBP) are basic region/leucine zipper (bZIP) transcription factors selectively expressed during the differentiation of liver, adipose tissue, blood cells, and the endocrine pancreas. Here we show that C/EBP isoforms are differentially expressed in the skin. BALB/MK keratinocytes incubated in 0.12 mM calcium medium undergo a differentiation program featuring growth-arrest at 24-48 h, keratin K10 gene expression beginning at 24 h, and apoptosis commencing at 48 h. Within this framework, western immunoblot analysis and immunohistochemistry reveal that C/EBP alpha increases 5-fold at 1-2 d and remains elevated, C/EBP beta rises 2-fold at 2-4 d and gradually falls, and CHOP rises 9-fold in the first 24 h then returns rapidly to baseline. Several products of alternative translation are observed in BALB/MK cells, i.e., 42 kDa and 30 kDa forms of C/EBP alpha, and 32 kDa and 20 kDa forms of C/EBP beta. By immunohistologic examination of human, rat, and mouse skin, all three transcription factors are highly expressed within epithelial compartments in a spatially restricted distribution. C/EBP alpha is concentrated in the upper epidermis in a predominantly cytoplasmic location within cells, whereas the highest levels of C/EBP beta and CHOP are seen in the mid-epidermis, mainly within nuclei. High levels of C/EBP beta and CHOP (but not C/EBP alpha) are also observed in hair follicles and sebaceous glands. The identity of these factors in the epidermis is confirmed by western immunoblot analyses. In summary, C/EBP are expressed in a differentiation-associated manner in the skin, and may play an important role in regulating one or more aspects of the epidermal differentiation program.
CCAAT 增强子结合蛋白（C/EBP）是碱性区域/亮氨酸拉链（bZIP）转录因子，在肝脏、脂肪组织、血细胞和内分泌胰腺的分化过程中选择性表达。在此我们表明，C/EBP 亚型在皮肤中差异表达。在 0.12 mM 钙培养基中培养的 BALB/MK 角质形成细胞经历一个分化程序，其特征为在 24 - 48 小时生长停滞，角蛋白 K10 基因在 24 小时开始表达，凋亡在 48 小时开始。在此框架内，蛋白质免疫印迹分析和免疫组织化学显示，C/EBPα在 1 - 2 天增加 5 倍并保持升高，C/EBPβ在 2 - 4 天升高 2 倍然后逐渐下降，而 CHOP 在最初 24 小时升高 9 倍然后迅速恢复到基线。在 BALB/MK 细胞中观察到几种可变翻译产物，即 42 kDa 和 30 kDa 形式的 C/EBPα，以及 32 kDa 和 20 kDa 形式的 C/EBPβ。通过对人、大鼠和小鼠皮肤的免疫组织学检查，所有这三种转录因子在上皮区室中以空间受限的分布高度表达。C/EBPα集中在上表皮细胞内主要位于细胞质的位置，而 C/EBPβ和 CHOP 的最高水平见于表皮中部，主要在细胞核内。在毛囊和皮脂腺中也观察到高水平的 C/EBPβ和 CHOP（但不是 C/EBPα）。这些因子在表皮中的身份通过蛋白质免疫印迹分析得以证实。总之，C/EBP 在皮肤中以与分化相关的方式表达，并可能在调节表皮分化程序的一个或多个方面发挥重要作用。
