Kitagawa Norio, Inai Yuko, Higuchi Yoshinori, Iida Hiroshi, Inai Tetsuichiro
Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, 814-0193, Japan.
Histochem Cell Biol. 2014 Oct;142(4):389-99. doi: 10.1007/s00418-014-1219-9. Epub 2014 Apr 9.
Epidermal keratinocytes proliferate in the basal layer, differentiate, migrate through the spinous layer, granular layer and cornified layer, and finally are peeled off from the surface of skin with layer-specific expression of differentiation markers, including cytokeratins and cell-cell junction proteins such as desmogleins. Basal cells express CK5, CK14 and Ki67. In contrast, the suprabasal cells in the spinous and granular layers express CK1 and CK10 without Ki67. Inhibition of c-Jun NH2-terminal protein kinase (JNK) in HaCaT cells, a human epidermal keratinocyte cell line, induced the formation of tight junctions, which occurs in the granular layer in vivo. These cells lost their expression of CK5 and CK17, exhibited decreased expression of desmoglein 3 and had no Ki67 labeling in the nucleus. These results suggest that inhibition of JNK causes HaCaT cells to differentiate from basal- and spinous-like cells to granular-like cells. The inhibition of JNK in HaCaT cells provides a useful in vitro model system to study the differentiation of epidermal keratinocytes.
表皮角质形成细胞在基底层增殖、分化，穿过棘层、颗粒层和角质层迁移，最终从皮肤表面脱落，同时伴随着包括细胞角蛋白和细胞间连接蛋白（如桥粒芯糖蛋白）等分化标志物的层特异性表达。基底细胞表达CK5、CK14和Ki67。相比之下，棘层和颗粒层的基底上层细胞表达CK1和CK10，但不表达Ki67。在人表皮角质形成细胞系HaCaT细胞中抑制c-Jun氨基末端蛋白激酶（JNK）可诱导紧密连接的形成，这一过程在体内发生于颗粒层。这些细胞失去了CK5和CK17的表达，桥粒芯糖蛋白3的表达降低，并且细胞核中没有Ki67标记。这些结果表明，抑制JNK会使HaCaT细胞从基底样和棘层样细胞分化为颗粒样细胞。在HaCaT细胞中抑制JNK为研究表皮角质形成细胞的分化提供了一个有用的体外模型系统。
