Inactivation of mitogen-activated protein kinase signaling pathway reduces caspase-14 expression in impaired keratinocytes.
OBJECTIVE
Several investigations have revealed that caspase-14 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-14 in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the possible mechanism that contributes to the regulation of caspase-14.


METHODS
The filaggrin-deficient NHEKs were induced by transfection with lentivirus (LV) vector encoding small hairpin RNAs (shRNA). The inhibitors SB203580, PD98059 and SP600125 were used for suppressing the expression of p38 mitogen-activated protein kinase (MAPK), p44/42 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The expression of filaggrin, p38 MAPK, p44/42 MAPK and SAPK/JNK, caspase-14, keratin1and keratin2 were detected by western blot.


RESULTS
In filaggrin-deficient NHEKs, the expression of p38, p44/42 MAPK and SAPK/JNK and caspase-14 were significantly decreased. The inhibition of p38 and SAPK/JNK reduced the expression of caspase-14, while the p44/42 MAPK showed no consistent effects. Moreover, the filaggrin knockdown decreased the expression of keratin2, but had no effects on the level of keratin1.


CONCLUSIONS
The decreased expression of caspase-14 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-14 on skin barrier function.
Department of Dermatology, Jinan Central Hospital affiliated to Shandong University, Jinan, Shandong Province, 250013, China; College of Life Science, Shandong Normal University, Jinan Shandong Province, 250014, China.
Ningning
N
Dang
Department of Endocrinology, Jinan Central Hospital affiliated to Shandong University, Jinan, Shandong Province, 250013, China.
Shuguang
S
Pang
Department of Dermatology, Jinan Central Hospital affiliated to Shandong University, Jinan, Shandong Province, 250013, China.
Haiyan
H
Song
College of Life Science, Shandong Normal University, Jinan Shandong Province, 250014, China.
Liguo
L
An
Central Laboratory, Jinan Central Hospital affiliated to Shandong University, Jinan, Shandong Province, 250013, China.
Xiaoli
X
Ma
Caspase-14; Filaggrin; MAPK signaling pathway Skin barrier