Retinoic acid disintegrated desmosomes and hemidesmosomes in stratified oral keratinocytes

Abstract

Although it is known that retinoic acid (RA) regulates the cellular differentiation of skin keratinocytes, the effects of RA on the anchoring junction have not been clarified. The effects of all-trans RA on cell-cell and cell-matrix connections of gingival epithelial (GE)1 cells in a multilayered culture were investigated. Ultrastructures of GE1 cells were observed and immunohistochemistry was used to detect keratin 4, keratin 13, and desmoglein expression. Reverse transcription-polymerase chain reaction was performed to detect expression of desmosome and hemidesmosome-associating adhesion molecules, keratin 13, and keratin14. Retinoic acid caused immunohistochemical diminution of keratin 4, keratin 13, and desmoglein. Ultrastructurally, RA induced drastic loss of typical desmosomes and complete loss of hemidesmosomes. RA significantly decreased the transcript levels of keratin 13, keratin 14, desmoglein 1, and desmocollin 1 in a dose-dependent manner. The 230-kD bullous pemphigoid antigen (BPAG1) gene expression was also reduced by RA, whereas transcript levels of integrin alpha6, integrin beta4, the 180-kD bullous pemphigoid antigen (BPAG2), and laminin 5 were not affected. These results indicated that RA disintegrated not only desmosomes by depriving the cells of desmoglein 1, desmocollin 1, keratin 13, and keratin 4, but also hemidesmosomes by reducing the expression of BPAG1 and keratin 14 in basal keratinocytes.