Overexpression of Wilms' tumor 1 in skin lesions of psoriasis is associated with abnormal proliferation and apoptosis of keratinocytes

  • Authors:
    • Ruifang Wu
    • Yuan Liao
    • Weiyun Shen
    • Yu Liu
    • Jianzhong Zhang
    • Min Zheng
    • Genghui Chen
    • Yuwen Su
    • Ming Zhao
    • Qianjin Lu
  • View Affiliations

  • Published online on: August 16, 2018     https://doi.org/10.3892/mmr.2018.9391
  • Pages: 3973-3982
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Abstract

Psoriasis vulgaris (PV) is a chronic inflammatory skin disease, which is characterized by the abnormal proliferation and apoptosis of keratinocytes. Previous studies have demonstrated that transcription factor Wilms' tumor 1 (WT1) is involved in a number of pathophysiological processes, including organ development, tumorigenesis and cell proliferation. However, the role of WT1 in PV remains unclear. In the present study, WT1 expression was analyzed by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. WT1 was stably overexpressed or inhibited in HaCaT cells using Lipofectamine® 2000, and cell proliferation and apoptosis were determined using a Cell Counting Kit‑8 or Fluorescein Isothiocyanate Annexin V Apoptosis Detection kit II, respectively. We demonstrated that compared with normal controls, the mRNA and protein expression levels of WT1 were significantly increased in non‑lesional skins (human, P<0.0001 and P=0.0291, respectively; mouse, P=0.0020 and P=0.0150, respectively) and lesional skins (human, P<0.0001 and P=0.0060, respectively; mouse, P=0.0010 and P=0.0172, respectively) of patients with PV, in addition to the imiquimod (IMQ)‑induced psoriasis‑like mouse model. WT1 mRNA and protein expression levels in lesional skins were slightly increased compared with those in non‑lesional skins from patients with psoriasis (P=0.2510 and P=0.1690, respectively) and IMQ‑treated mice (P=0.9590 and P=0.2552, respectively), although there were no statistical differences. Knockdown of WT1 inhibited the proliferation of HaCaT cells [day (D)4, P=0.0454; D5, P=0.0021] and promoted their apoptosis (P=0.0007), while overexpressing WT1 exhibited the opposite effects (proliferation D3, P=0.0216; D4, P=0.0356; D5, P=0.0188; apoptosis, P=0.0003). Furthermore, it was identified that the inflammatory cytokines interleukin‑17A (IL‑17A), interferon‑γ and IL‑22 induced the overexpression of WT1 in HaCaT cells. The results of the present study suggested that inflammatory cytokine‑induced WT1 overexpression may promote the formation of psoriatic skin lesions via regulation of the proliferation and apoptosis of keratinocytes.

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APA
Wu, R., Liao, Y., Shen, W., Liu, Y., Zhang, J., Zheng, M. ... Lu, Q. (2018). Overexpression of Wilms' tumor 1 in skin lesions of psoriasis is associated with abnormal proliferation and apoptosis of keratinocytes. Molecular Medicine Reports, 18, 3973-3982. https://doi.org/10.3892/mmr.2018.9391
MLA
Wu, R., Liao, Y., Shen, W., Liu, Y., Zhang, J., Zheng, M., Chen, G., Su, Y., Zhao, M., Lu, Q."Overexpression of Wilms' tumor 1 in skin lesions of psoriasis is associated with abnormal proliferation and apoptosis of keratinocytes". Molecular Medicine Reports 18.4 (2018): 3973-3982.
Chicago
Wu, R., Liao, Y., Shen, W., Liu, Y., Zhang, J., Zheng, M., Chen, G., Su, Y., Zhao, M., Lu, Q."Overexpression of Wilms' tumor 1 in skin lesions of psoriasis is associated with abnormal proliferation and apoptosis of keratinocytes". Molecular Medicine Reports 18, no. 4 (2018): 3973-3982. https://doi.org/10.3892/mmr.2018.9391