Knockdown of filaggrin influences the epidermal terminal differentiation via MAPK pathway in normal human epidermal keratinocytes.

We aimed to gain further insight into the role of the MAPK signaling pathway in terminal differentiation of normal human epidermal keratinocytes (NHEKs) with filaggrin knockdown. Filaggrin expression was knocked down by shRNA technology and the MAPK pathways were inhibited by three different inhibitors in NHEKs. The associated mRNAs and proteins were investigated by RT-PCR and western blot. Filaggrin absence inhibited the expression of differentiation-associated proteins, and blocked the protein expression of p38 MAPK, ERK1/2, JNK, Akt and NF-κB. Moreover, inhibited p38 MAPK, instead of ERK1/2 or JNK, lead to decreases in the expressions of Akt, NF-κB, and differentiation- associated proteins. In conclusion, Filaggrin might affect the epidermal terminal differentiation mainly through the p38-MAPK, NF-κB and Akt pathways. ERK1/2 and JNK might also be involved in the process.