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

Shuai ZHANG; Wen LUO; Lian ZHANG; Xiuqin YIN; Hong LUO

doi:10.16016/j.2097-0927.202302004

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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

Clinical Medicine | 更新时间：2026-01-09

- 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
- Journal of Army Medical University Vol. 46, Issue 6, Pages: 637-643(2024)
- 作者机构：
  
  410000 长沙，长沙市第一医院皮肤科
- 作者简介：
- 基金信息：
  
  the Project of Scientific Research Plan of Hunan Provincial Health Commission(202204122971)
- DOI：10.16016/j.2097-0927.202302004
  CLC： R322.99;R394.3;R758.63
- Received：01 February 2023，
  
  Revised：2023-08-23，
  
  Published：30 March 2024
- 稿件说明：
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Shuai ZHANG, Wen LUO, Lian ZHANG, et al. 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[J]. Journal of Army Medical University, 2024, 46(6): 637-643.
DOI：

Shuai ZHANG, Wen LUO, Lian ZHANG, et al. 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[J]. Journal of Army Medical University, 2024, 46(6): 637-643. DOI： 10.16016/j.2097-0927.202302004.

摘要

目的

探讨银屑病患者皮损组织中Krüppel样因子4(Krüppel-like factor 4

KLF)异常高表达的DNA甲基化分子机制。

方法

以20例寻常型银屑病患者病理检查所取皮损组织为实验组，13例眼外伤手术患者所取眼睑皮肤组织为对照组。采用亚硫酸氢盐测序(bisulfite sequencing

BSP)检测各组皮肤样本及转染十-十一转位3(ten-eleven translocation 3

TET3)过表达及干扰质粒的人永生化角质形成细胞HaCat中转录因子Krüppel样因子4(Krüppel-like factor 4

KLF4)启动子区DNA甲基化水平，RT-qPCR和Western blotting检测各组皮肤组织样本及转染HaCat细胞中KLF4、TET1(ten-eleven translocation1)、TET2、TET3的表达水平。

结果

实验组KLF4启动子DNA甲基化水平显著低于对照组(

0.01)，实验组KLF4的mRNA表达水平显著高于对照组(

0.01)。实验组KLF4启动子DNA甲基化水平与mRNA表达水平呈显著负相关(

=-0.649，

=0.002)。实验组TET3表达水平显著高于对照组(

0.01)

TET1及TET2表达水平差异无统计学意义。实验组TET3表达水平与KLF4启动子DNA甲基化水平呈显著负相关(

=-0.688，

=0.001)。HaCat细胞中过表达TET3后，KLF4启动子DNA甲基化水平明显下调(

0.01)，KLF4表达水平显著上调(

0.01)。HaCat细胞中干扰TET3表达后，KLF4启动子DNA甲基化水平明显上调(

0.01)，KLF4表达水平显著下调(

0.01)。

结论

过度表达的TET3通过下调KLF4启动子DNA甲基化水平，介导银屑病患者皮损组织中KLF4过度表达。

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 (

0.01)

and the KLF4 mRNA level was obviously higher in the experimental group than the control group (

0.01). A negative correlation was observed between DNA methylation level of KLF4 promoter and KLF4 mRNA level in the experimental group (

=-0.649

=0.002). The experimental group had notably higher expression level of TET3 (

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 (

=-0.688

=0.001). After overexpression of TET3 in HaCat cells

the DNA methylation level of KLF4 promoter was significantly decreased (

0.01)

and KLF4 expression level was obviously increased (

0.01). After interfering with TET3 expression in HaCat cells

the DNA methylation level of KLF4 promoter was notably up-reg

ulated (

0.01)

and the KLF4 expression level was remarkably decreased (

0.01).

Conclusion

Overexpression of TET3 mediates the overexpression of KLF4 in psoriatic lesions by down-regulating the DNA methylation level of KLF4 promoter.

关键词

Keywords

references

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