title: Wnt/β-Catenin and Wnt5a/Ca Pathways Regulate Proliferation and Apoptosis of Keratinocytes in Psoriasis Lesions.
abstract: Wnt5a is overexpressed in psoriasis lesions, however the mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not clear. To address this, the expression of Wnt5a in psoriatic lesions and its effect on keratinocyte cell proliferation and apoptosis was examined in vitro.
  
  
  METHODS
  The expression levels of WNT5A, and genes encoding its receptors frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short interfering (si)RNAs was performed in cultured HaCaT keratinocytes and normal human keratinocytes (NHK), and the expression of Wnt5a, protein kinase C (PKC), and β-catenin were determined, and cell cycle activity, proliferation and apoptosis were assessed.
  
  
  RESULTS
  The expression of WNT5A, FZD2 and FZD5 mRNA and protein were increased in psoriatic lesions. Wnt5a knockdown suppressed proliferation and induced apoptosis in HaCaT and NHK cells. Additionally, expression of PCNA, MKI67, CCND1, BCL2, CTNNB1, and genes encoding PKC and survivin were downregulated, whereas CASP3 was upregulated. The mRNA levels of the Wnt pathway inhibitors DKK1 and SFRP1 were upregulated, Western blotting analyses demonstrated reduction in β-catenin and PKC protein levels.
  
  
  CONCLUSIONS
  Knockdown of Wnt5a suppresses the proliferation of keratinocytes and induces apoptosis by inhibiting the Wnt/β-catenin or Wnt5a/Ca(2+) pathways.
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Tu
authors.forename: Dingwei
authors.initials: D
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Peng
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Feng
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Xiao
authors.forename: Zhengxiao
authors.initials: Z
authors.lastname: Li
mesh_terms: D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D051157:Frizzled Receptors / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C489742:FZD2 protein, human; C498589:FZD5 protein, human; D051157:Frizzled Receptors; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; D011493:Protein Kinase C; D002118:Calcium