Potential Role of Cytosolic RNA Sensor MDA5 as an Inhibitor for Keratinocyte Differentiation in the Pathogenesis of Psoriasis

ABSTRACT

Background@#Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. @*Objective@#The purpose of this study is to uncover possible roles of MDA5 in psoriasis. @*Methods@#Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. @*Results@#As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(IC) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(IC)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. @*Conclusion@#These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.