Molecular Mechanism of KLF4 Up-regulating Keratin 17 Expression in Keratinocytes

  Objective  To explore the role of Kruppel-like factor 4 (KLF4) in the regulation of Keratin 17 (KRT17) expression, and to reveal the molecular mechanism of overexpression of KRT17 in psoriatic lesions.

  Methods  The skin lesions of 18 patients with psoriasis vulgaris were taken as experimental group and 10 healthy persons as control group. Real time-PCR and Western blot were used to detect the expression of KLF4 in psoriasis and normal skin samples, and the changes of KRT17 expression in HaCat cells after transfection of KLF4 overexpression and EP300 interfering plasmid. ChIP-qPCR was used to detect KLF4 binding and histone H3 acetylation levels in the promoter region of KRT17 in psoriasis and normal skin samples, and the changes of KLF4 binding and histone H3 acetylation levels in the promoter region of KRT17 in HaCat cells after transfection of KLF4 overexpression and EP300 interfering plasmid. Co-IP detects the interaction between KLF4 and EP300.

  Results  The expression level of KLF4, KLF4 binding level and histone H3 acetylation level in the promoter region of KRT17 in psoriasis group were significantly higher than those in normal group (P<0.01). Compared with the control group, the expression level of KRT17 was significantly higher after KLF4 overexpression (P<0.01). After KLF4 overexpression combined with EP300 interference, the expression level of KRT17 was significantly lower than that of KLF4 overexpression group (P<0.01), slightly lower than that of control group (P<0.05). Compared with the control group, the histone H3 acetylation level in KRT17 promoter region in KLF4 over-expression group was increased significantly (P<0.01). After KLF4 over-expression combined with EP300 interference, the acetylation level of histone H3 in KRT17 promoter region was significantly lower than that in KLF4 overexpression group (P<0.01) and control group (P<0.01). Co-IP confirmed that KLF4 and EP300 could form protein complexes.

  Conclusion  Excessive KLF4 increases the level of histone H3 acetylation in KRT17 promoter region by synergistic EP300, and mediates the over-expression of KRT17 in psoriatic lesions.