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

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

Open Med (Wars). 2018 May 10:13:189-195. doi: 10.1515/med-2018-0029. eCollection 2018.

Authors

Xianguang Meng^{1

2}, Liyun Qiu³, Haiyan Song¹, Ningning Dang⁴

Affiliations

¹ Department of Dermatology, Jinan Central Hospital affiliated to Shandong University, Jinan 250013, Shandong Province, China.
² School of Medicine, Shandong University, Jinan Shandong Province, China.
³ Department of Pharmacy, Jinan Central Hospital affiliated to Shandong University, Jinan 250013, Shandong Province, China.
⁴ Department of Dermatology, Jinan Central Hospital affiliated to Shandong University, No.105 Jiefang Road, Jinan 250013, Shandong Province, China, Tel: +86-0531-85695173.

Abstract

Objective: To investigate the effect of mitogen-activated protein kinase (MAPK) signaling pathway in epidermal terminal differentiation.

Methods: The 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).

Results: Inhibition 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.

Conclusion: MAPK pathways regulates epidermal terminal differentiation in NHEKs. The p38 signaling pathway plays an especially important role.

Keywords: Differentiation-related proteins; Epidermal terminal differentiation; Keratinocyte differentiation; MAPK signaling pathway; Normal human epidermal keratinocytes (NHEKs).