Okada Yuka, Senba Emiko, Shirai Kumi, Ueyama Tekashi, Reinach Peter, Saika Shizuya
Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan.
Jpn J Ophthalmol. 2008 Jan-Feb;52(1):1-7. doi: 10.1007/s10384-007-0499-1. Epub 2008 Mar 28.
AP-1 is a transcription factor that plays a pivotal role in regulating cellular homeostasis and which may modulate the differentiation of corneal epithelial cells. We examined the role of c-Fos in the differentiation of corneal epithelial cells by using c-Fos-deficient (c-fos (-/-)) mice.
Ten adult c-fos (-/-) mice and ten control (c-fos (+/-) or c-fos (+/+)) mice were used. The expression patterns of the mRNA and protein of keratin 12 (K12) were determined to examine the differentiation of cornea-type epithelium. To evaluate the intraepithelial differentiation from basal cells to superficial cells, the ultrastructure of the corneal epithelium was studied. We focused on the formation of desmosomes in the superficial, suprabasal, and basal cell layers, and also on the hemidesmosomes. The number of desmosomes in each epithelial layer was statistically analyzed by using an unpaired t test. The expressions of keratin 14 (K14), desmoglein, E-cadherin, occludin, connexin 43, filaggrin, loricrin, and involucrin were examined to analyze epithelial differentiation.
The mRNA and protein of K12 were expressed in the corneal epithelium of c-fos (-/-) and control mice. Ultrastructural observations showed that the number of desmosomes between the basal cells of the corneal epithelia was similar in c-fos (-/-) and control mice. However, there were fewer desmosomes between suprabasal cells and between superficial cells in c-fos (-/-) mice than in control mice. The number of hemidesmosomes in the corneal epithelial cells in c-Fos-null mice was similar to that in control mice. The expressions of the other epithelial cell differentiation markers were not affected by the absence of c-Fos. Ultrastructural observations showed a disarrangement of the corneal epithelium in the c-Fos-null mice.
The absence of c-Fos disturbs the formation of desmosomes in the superficial layers of the corneal epithelium, suggesting a perturbation of intraepithelial differentiation from the basal epithelial cells to the suprabasal and superficial epithelial cells.
AP-1是一种转录因子，在调节细胞内稳态中起关键作用，且可能调节角膜上皮细胞的分化。我们通过使用c-Fos基因缺陷（c-fos(-/-)）小鼠来研究c-Fos在角膜上皮细胞分化中的作用。
使用10只成年c-fos(-/-)小鼠和10只对照（c-fos(+/-)或c-fos(+/+)）小鼠。测定角蛋白12（K12）的mRNA和蛋白质的表达模式，以检查角膜型上皮的分化。为评估从基底细胞到表层细胞的上皮内分化，研究了角膜上皮的超微结构。我们重点关注表层、基底上层和基底细胞层中桥粒的形成，以及半桥粒。使用不成对t检验对每个上皮层中桥粒的数量进行统计学分析。检测角蛋白14（K14）、桥粒芯糖蛋白、E-钙黏蛋白、闭合蛋白、连接蛋白43、丝聚蛋白、兜甲蛋白和内披蛋白的表达，以分析上皮分化。
K12的mRNA和蛋白质在c-fos(-/-)小鼠和对照小鼠的角膜上皮中均有表达。超微结构观察表明，c-fos(-/-)小鼠和对照小鼠角膜上皮基底细胞之间的桥粒数量相似。然而，c-fos(-/-)小鼠基底上层细胞之间和表层细胞之间的桥粒比对照小鼠少。c-Fos基因缺失小鼠角膜上皮细胞中的半桥粒数量与对照小鼠相似。其他上皮细胞分化标志物的表达不受c-Fos缺失的影响。超微结构观察显示c-Fos基因缺失小鼠的角膜上皮排列紊乱。
c-Fos的缺失扰乱了角膜上皮表层中桥粒的形成，提示从基底上皮细胞到基底上层和表层上皮细胞的上皮内分化受到干扰。
