Investigation of the Multiple Functional Roles of IFI27 in Psoriasis and Development of Anti-Psoriatis Drug by IFI27-siRNA

Psoriasis is a multifactorial hyperproliferative inflammatory skin disease characterized by hyperproliferation of keratinocytes, aberrant epidermal differentiation, angiogenesis and infiltration of inflammatory cells. IFI27, belonged to a family of small interferon-alpha (IFN-α)-inducible genes, was first reported over-expressed in breast carcinoma in 1993, and following studies also demonstrated the significant increase of IFI27 expression in psoriasis and certain epithelial cancers. Although it is highly speculated that IFI27 might be a marker for the proliferation of skin keratinocytes, the function of IFI27 has not yet been fully investigated. Our experimental results showed that the IFI27 expression of epidermal keratinocytes could be induced time- and dose-dependently by EGF and TNF-α, two major factors found to be significantly increased in psoriatic patients. IFI27 knockdown in epidermal keratinocytes resulted in S-phase arrest that was mediated by the impaired formation of CDK1 and cyclin A. Over-expression of IFI27 in keratinocytes, on the other hand, accelerated the cell proliferation rate, confirming the proliferating function of IFI27 in keratinocytes which should play an important role in the pathogenesis of psoriasis. In addition, we have successfully established the imiquimod-induced psoriasis in mice model and our data showed that treatment with IFI27-siRNA might also have anti-inflammatory and anti-angiogenic effects. Therefore, we proposed this two-year study: 1st year--The multiple roles of IFI27 will be further studied. Except cell proliferation, how IFI27 regulates angiogenesis and infiltration of inflammatory cells will be investigated, particularly the relation with epiregulin, TGF-alpha, keratin 17和IL-8. 2nd year--The therapeutic efficacy of IFI27-siRNA using different delivery methods will be investigated on imiquimod-induced mice model and the expression of the above genes will be analyzed in skin lesions. This study will help us to understand the function of IFI27 in psoriasis and based on this understanding, hopefully, we can develop a better IFI27-targeted therapy for psoriasis.

Project ID:PC10408-2345
External Project ID:MOST104-2314-B182-039