MAPK pathway involved in epidermal terminal differentiation of normal human epidermal keratinocytes

AbstractObjectiveTo investigate the effect of mitogen-activated protein kinase (MAPK) signaling pathway in epidermal terminal differentiation.MethodsThe MAPK pathways (p38, ERK1/2, JNK) were inhibited by SB203580, PD98059, and SP600125 in normal human epidermal keratinocytes (NHEKs), respectively. Western blotting assays were performed to detect expression of filaggrin and differentiation-related proteins. The mRNA expressions of differentiation-related proteins were detected by real-time quantitative PCR (qRT-PCR).ResultsInhibition of MAPK pathway by SB203580, PD98059, and SP600125 resulted in significant reduction of filaggrin expression in NHEKs. Inhibition of the p38 MAPK pathway decreased the expression of differentiation-related proteins (cytokeratin 5, cytokeratin 14, ST14, and SPRR3), Akt, and NF-κB. Inhibition of JNK also suppressed expression of cytokeratin 14, SPRR3, Akt, and NF-κB. However, inhibition of ERK1/2 merely decreased expression of SPRR3 and Akt.ConclusionMAPK pathways regulates epidermal terminal differentiation in NHEKs. The p38 signaling pathway plays an especially important role.

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

médecine/sciences ◽

10.1051/medsci/201834f116 ◽

2018 ◽

Vol 34 ◽

pp. 94-98 ◽

Cited By ~ 1

Author(s):

Shumei Wang ◽

Liyun Qiu ◽

Xianguang Meng ◽

Ningning Dang

Keyword(s):

Signaling Pathway ◽

Terminal Differentiation ◽

Mapk Signaling ◽

Epidermal Keratinocytes ◽

Structural Protein ◽

Human Epidermal Keratinocytes ◽

Knock Down ◽

Normal Human Epidermal Keratinocytes ◽

Normal Human ◽

Related Proteins

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.

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