MAPK Pathway Involved in Epidermal Terminal Differentiation of Normal Human Epidermal Keratinocytes.

Xianguang Meng,Liyun Qiu,Haiyan Song,Ningning Dang

doi:10.1515/med-2018-0029

Abstract

ObjectiveTo 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.

Highlights

Skin is the first line of defense for the human body to resist environmental damage, water and nutrients loss, and prevent pathogens and allergens from entering
Inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway decreased the expression of differentiation-related proteins, Akt, and NF-κB
To examine whether MAPK pathways had an effect on filaggrin expression, we cultured normal human epidermal keratinocytes (NHEKs) cells with a specific inhibitor (SB203580) of the p38 MAPK pathway, a specific inhibitor (PD98059) of ERK1/2 pathway, and a specific inhibitor (SP600125) of JNK pathway

Summary

Introduction

Skin is the first line of defense for the human body to resist environmental damage, water and nutrients loss, and prevent pathogens and allergens from entering. The MAPK families have been proven to be essential for controlling diverse cellular behaviors, including cell proliferation, differentiation and apoptosis, for instance the p38 MAPK pathway, ERK1/2 MAPK pathway and JNK signaling pathway [3, 4]. Studies have shown that the MAPK signaling pathways integrate and mediate various signals and play a major role in regulating keratinocyte differentiation and the function of skin barrier [5,6,7]. The ERK1/2 signaling pathway has been shown to control keratinocyte differentiation; low ERK1/2 activity could induce keratinocyte differentiation and apoptosis [8]. The p38 and ERK pathways are activated and participate in keratinocyte differentiation among MAPK signaling pathways while the epidermal barrier is disrupted [8,9,10,11]. Epidermal differentiation would be enhanced when JNK is inhibited by SP600125 [11]

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Discussion

Conclusion