DUSP1/MKP-1 regulates proliferation and apoptosis in keratinocytes through the ERK/Elk-1/Egr-1 signaling pathway.

Abstract:

:Psoriasis is an inflammatory skin disease with preference for the skin and joints that occurs due to hyper-proliferation and abnormal apoptosis of keratinocytes. DUSP1 expression in dermal mesenchymal stem cells (MSCs) is obviously lower in psoriasis patients than that in healthy individuals. The present study aimed to explore the roles of DUSP1 in the proliferation and apoptosis of HaCaT cells treated with a cocktail of M5. We showed that DUSP1 was markedly reduced in psoriasis patients and M5-treated HaCaT cells compared with the control subjects. MTT and BrdU assays revealed that overexpression of DUSP1 significantly suppressed the proliferation of HaCaT cells. Furthermore, DUSP1 decreased M5-induced the upregulation of cyclin D1 and Rb. In addition, we demonstrated that forced overexpression of DUSP1 caused an augment of cell apoptosis rate, c-caspase 3 protein level and the Bax/Bcl-2 ratio. Finally, we determined that enhancing DUSP1 expression resulted in the reduction of p-ERK, p-Elk-1 and Egr-1 protein levels using western blot, and the Chromatin immunoprecipitation (ChIP) assay displayed that p-Elk-1 binds to the promoter of Egr-1 in HaCaT cells. The roles of DUSP1 in cell proliferation and apoptosis were abolished by overexpression of Egr-1. In summary, gain function of DUSP1 regulates proliferation and apoptosis of HaCaT cells through the ERK/Elk-1/Egr-1 signaling pathway.

journal_name

Life Sci

journal_title

Life sciences

authors

Yang J,Sun L,Han J,Zheng W,Peng W

doi

10.1016/j.lfs.2019.03.018

subject

Has Abstract

pub_date

2019-04-15 00:00:00

pages

47-53

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(19)30176-6

journal_volume

223

pub_type

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