Knock-down of filaggrin influences the mitogen-activated protein kinases signaling pathway in normal human epidermal keratinocytes.

BACKGROUND

Filaggrin is an essential structural protein of the stratum corneum binding to the keratin intermediate filaments to form a dense protein-lipid matrix. However, the function of filaggrin in epidermal terminal differentiation is not completely understood.

AIM

To evaluate the effects of filaggrin on normal human epidermal keratinocytes (NHEKs) and to investigate the relevant mechanisms.

METHODS

Short hairpin RNA (shRNA) technology was used to knock-down filaggrin in normal human epidermal keratinocytes (NHEKs). Western blot and real-time quantitative PCR (qRT-PCR) were performed to detect expression of filaggrin, differentiation-related proteins and MAPK-related proteins.

RESULTS

Filaggrin was successfully knocked down in NHEKs (99% efficiency). We found that the lack of filaggrin significantly decreased the expression of some differentiation-related proteins, including Cytokeratin 5 protein, Cytokeratin 14 protein, ST14 protein and SPRR3 protein (P<0.05). In addition, filaggrin knock-down significantly decreased expression of p-p38, p-ERK1/2, p-JNK, p-Akt, and p-NF-κB in NHEKs.

CONCLUSION

Our study shows that filaggrin regulates epidermal terminal differentiation and impairs MAPK signaling pathway in normal human epidermal keratinocytes.