IFI27, a novel epidermal growth factor‐stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes. (9th February 2015)

• Record Type: Journal Article
• Authors: Hsieh, W.‐L.; Huang, Y.‐H.; Wang, T.‐M.; Ming, Y.‐C.; Tsai, C.‐N.; Pang, J.‐H. S.
• Is Part Of: Cell proliferation. Volume 48:Number 2(2015:Apr.)
• Page Start: 187
• Page End: 197
• Publication Date: 2015-02-09
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12168
• Languages: English
• ISSNs: 0960-7722

Abstract

<abstract abstract-type="main" id="cpr12168-abs-0001"> <title>Abstract</title> <sec id="cpr12168-sec-0001" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="cpr12168-sec-0002" sec-type="section"> <title>Materials and methods</title> <p>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 <italic>in vivo</italic> by topical application of IFI27 siRNA on imiquimod‐induced psoriatic lesions, in a mouse model.</p> </sec> <sec id="cpr12168-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="cpr12168-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Our study demonstrates for the first time, that cell function of IFI27 is involved in proliferation of skin keratinocytes both <italic>in vitro</italic> and <italic>in vivo</italic>. It suggests that IFI27 might be a suitable target for development of a novel anti‐psoriasis therapy.</p> </sec> </abstract>