Overexpression of DNA demethylase ten-eleven translocation 3 mediates high expression of Krüppel-like factor 4 in the skin lesions of patients with psoriasis vulgaris

Abstract

Objective To investigate the molecular mechanism of DNA methylation of the abnormally high expression of Krüppel-like factor 4 (KLF4) in psoriasis vulgaris lesions. Methods The skin lesions of 20 patients with psoriasis vulgaris were taken as experimental group and those from 13 healthy individuals as control group. Bisulfite sequencing (BSP) was used to detect the DNA methylation of KLF4 promoter in the skin samples and in HaCat cells with ten-eleven translocation 3 (TET3) overexpression and interference, respectively. Real time PCR and Western blotting were employed to detect the expression levels of KLF4, TET1, TET2 and TET3 in skin samples and transfected HaCat cells. Results The DNA methylation level of KLF4 promoter was significantly lower (P < 0.01), and the KLF4 mRNA level was obviously higher in the experimental group than the control group (P < 0.01). A negative correlation was observed between DNA methylation level of KLF4 promoter and KLF4 mRNA level in the experimental group (r=-0.649, P=0.002). The experimental group had notably higher expression level of TET3 (P < 0.01), but had no differences in the levels of TET1 and TET2 when compared with the control group. The expression level of TET3 was negatively correlated with the DNA methylation level of KLF4 promoter in the experimental group (r=-0.688, P=0.001). After overexpression of TET3 in HaCat cells, the DNA methylation level of KLF4 promoter was significantly decreased (P < 0.01), and KLF4 expression level was obviously increased (P < 0.01). After interfering with TET3 expression in HaCat cells, the DNA methylation level of KLF4 promoter was notably up-regulated (P < 0.01), and the KLF4 expression level was remarkably decreased (P < 0.01). Conclusion Overexpression of TET3 mediates the overexpression of KLF4 in psoriatic lesions by down-regulating the DNA methylation level of KLF4 promoter.

Keywords

• psoriasis
• keratinocyte
• dna methylation
• ten-eleven translocation 3
• krüppel-like factor 4