Ann Dermatol.  2021 Aug;33(4):339-344. 10.5021/ad.2021.33.4.339.

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

• Hong DK
• Choi MR
• Hwang YL
• Lee JK
• Lee Y
• Seo YJ
• Kim S
• Lee YH
• Kim CD
• Lee JH

• KMID: 2517840
• DOI: http://doi.org/10.5021/ad.2021.33.4.339

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(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-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.

Keyword

Differentiation; Keratinocytes; MDA5; Psoriasis