Inhibition of JNK in HaCaT cells induced tight junction formation with decreased expression of cytokeratin 5, cytokeratin 17 and desmoglein 3.
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.
Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, 814-0193, Japan.
Norio
N
Kitagawa
Yuko
Y
Inai
Yoshinori
Y
Higuchi
Hiroshi
H
Iida
Tetsuichiro
T
Inai
D000873:Anthracenes / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D051184:Desmoglein 3 / Q000096:biosynthesis* / Q000172:deficiency; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053537:Keratin-17 / Q000096:biosynthesis* / Q000172:deficiency; D053555:Keratin-5 / Q000096:biosynthesis*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
D000873:Anthracenes; C071894:DSG3 protein, human; D051184:Desmoglein 3; D053537:Keratin-17; D053555:Keratin-5; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases