Background and aims Psoriasis vulgaris (PV) is a chronic inflammatory skin disease characterised by abnormal keratinocytes proliferation and apoptosis. Evidence has showed that transcription factor WT1 plays important role in many pathophysiologic processes such as organs development, tumorigenesis and cells proliferation. However, the role of WT1 in PV is still remain unclear. In this study, we will investigate the role of WT1 in the pathogenesis of lesion formation in PV.
Methods Skin specimens and peripheral blood mononuclear cells (PBMCs) were obtained from 25 patients with PV and 20 age- and sex-matched healthy subjects. mRNA and protein levels were detected by real-time RT-PCR and western blot. WT1 siRNA and WT1 overexpression plasmid were transfected into HaCaT cells with lipofectamine 2000 respectively. The proliferation and apoptosis of HaCaT cells were detected by CCK8 kit and Annexin V-FITC/PI Apoptosis Detection Kit .
Results Compared with normal controls, both the mRNA and protein level of WT1 were increased significantly in psoriatic skin and PBMCs. Transfect with WT1 siRNA inhibited the proliferation of HaCaT cells and promoted HaCaT cells apoptosis, while WT1 overexpression plasmid exhibited the opposite effects on HaCaT cells. The global DNA methylation level of psoriatic skins and PBMCs were elevated accompanied with increased DNMT1 expression. In addition, an positive correlation was observed between WT1 and DNMT1.
Conclusions Increased WT1 promotes the keratinocytes proliferation and inhibites the apoptosis of keratinocytes which may mediated by recruiting DNMT1 to its target genes related to cell proliferation and apoptotic pathway.
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