title: IFI27, a novel epidermal growth factor-stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes.
abstract: OBJECTIVE
  IFI27 is highly expressed in psoriatic lesions but its function has not been known. The present study aimed to explore its role in proliferation of epidermal keratinocytes.
  
  
  METHODS
  IFI27 knockdown and over-expression in keratinocytes were used to compare their proliferation, by MTT assay, apoptosis (by annexin V binding) and cell cycle progression by flow cytometry. Formation of cyclin A/CDK1 complex was examined by a co-immunoprecipitaion method. Anti-proliferation effects of IFI27 were also examined in vivo by topical application of IFI27 siRNA on imiquimod-induced psoriatic lesions, in a mouse model.
  
  
  RESULTS
  Epidermal growth factor was demonstrated to increase IFI27 expression by prolonging half-life of IFI27 protein. The IFI27 knockdown in keratinocytes reduced the proliferation rate, but had no effect on apoptosis nor on apoptosis-related genes. Interestingly, IFI27 knockdown resulted in S-phase arrest that was found to be associated with increased Tyr15 phosphorylation of CDK1, reduced CDC25B and reduced formation of cyclin A/CDK1 complex. In addition, IFI27 knockdown was also shown to activate p53 by Ser15 phosphorylation and increase p21 expression. Topical application of IFI27 siRNA on imiquimod-induced psoriatic lesion in a mouse model reduced epidermal thickness, formation of rete ridges and PCNA expression.
  
  
  CONCLUSIONS
  Our study demonstrates for the first time, that cell function of IFI27 is involved in proliferation of skin keratinocytes both in vitro and in vivo. It suggests that IFI27 might be a suitable target for development of a novel anti-psoriasis therapy.
authors: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan City, 33302, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan City, 33302, Taiwan.
authors: W-L
authors: WL
authors: Hsieh
authors: Y-H
authors: YH
authors: Huang
authors: T-M
authors: TM
authors: Wang
authors: Y-C
authors: YC
authors: Ming
authors: C-N
authors: CN
authors: Tsai
authors: J-H S
authors: JH
authors: Pang
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016203:CDC2 Protein Kinase; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D019925:Cyclin A / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D000077271:Imiquimod; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000096:biosynthesis; D010766:Phosphorylation; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics; D012867:Skin / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D019925:Cyclin A; D050759:Cyclin-Dependent Kinase Inhibitor p21; C406887:IFI27 protein, human; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D004815:Epidermal Growth Factor; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases; D000077271:Imiquimod