Inactivation of mitogen-activated protein kinase signaling pathway reduces caspase-۱۴ expression in impaired keratinocytes

Objective(s):Several investigations have revealed that caspase-۱۴ is responsible for the epidermal differentiation and cornification, as well as the regulation of moisturizing effect. However, the precise regulation mechanism is still not clear. This study was aimed to investigate the expression of caspase-۱۴ in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the possible mechanism that contributes to the regulation of caspase-۱۴. Materials and Methods:The filaggrin-deficient NHEKs were induced by transfection with lentivirus (LV) vector encoding small hairpin RNAs (shRNA). The inhibitors SB۲۰۳۵۸۰, PD۹۸۰۵۹ and SP۶۰۰۱۲۵ were used for suppressing the expression of p۳۸ mitogen-activated protein kinase (MAPK), p۴۴/۴۲ MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The expression of filaggrin, p۳۸ MAPK, p۴۴/۴۲ MAPK and SAPK/JNK, caspase-۱۴, keratin۱and keratin۲ were detected by western blot.  Results:In filaggrin-deficient NHEKs, the expression of p۳۸, p۴۴/۴۲ MAPK and SAPK/JNK and caspase-۱۴ were significantly decreased. The inhibition of p۳۸ and SAPK/JNK reduced the expression of caspase-۱۴, while the p۴۴/۴۲ MAPK showed no consistent effects. Moreover, the filaggrin knockdown decreased the expression of keratin۲, but had no effects on the level of keratin۱. Conclusion: The decreased expression of caspase-۱۴ in filaggrin-deficient NHEKs may be induced by the inactivation of MAPK signaling pathway. These provide a novel perspective to understand the mechanism for the protective effects of filaggrin and caspase-۱۴ on skin barrier function.

Keywords:

Caspase-۱۴ , Filaggrin , MAPK signaling pathway Skin barrier