Effect of Activating Transcription Factor 3 on Inflammatory Response and Differentiation of Keratinocytes
- Author:
Kyungmin KIM
1
;
Doyeon KIM
;
Jung-Min SHIN
;
Dongkyun HONG
;
Kyung Eun JUNG
;
Young-Joon SEO
;
Young LEE
;
Chang Deok KIM
Author Information
1. Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
- Publication Type:Original Article
- From:Korean Journal of Dermatology
2022;60(10):640-646
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:Pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune responses. Genetic background is one of the most important factors in disease pathogenesis. However, psoriasis-associated genes have not yet been fully identified. Activating transcription factor 3 (ATF3) is a member of the cyclic adenosine monophosphate responsive element-binding protein family of transcription factors, which may regulate epidermal keratinocytes.
Objective:We aimed to evaluate the effects of ATF3 on inflammation and differentiation of keratinocytes.
Methods:We evaluated the expression of ATF3 in polyinosinic:polycytidylic acid (poly[I:C])-treated keratinocytes. Subsequently, we compared ATF3 levels in psoriatic and normal skin using immunohistochemical staining. To illustrate the role of ATF3, we generated ATF3-overexpressing keratinocytes and ATF3-knockdown keratinocytes using a recombinant adenovirus. We investigated inflammation and differentiation of keratinocytes by measuring the mRNA levels of inflammatory cytokines and differentiation markers.
Results:Treatment of keratinocytes with poly(I:C) increased ATF3 expression in a time-dependent manner. Immunohistochemical staining showed that ATF3 expression was increased in the epidermis of psoriatic tissues. When ATF3 was overexpressed in keratinocytes using a recombinant adenovirus, poly(I:C)-induced inflammation was reduced. Conversely, ATF3 knockdown increased poly(I:C)-induced inflammation. Thus, ATF3 overexpression inhibited keratinocyte differentiation, while ATF3 knockdown promoted it.
Conclusion:ATF3 may be involved in the pathogenesis of psoriasis by influencing the inflammatory response and differentiation of keratinocytes.
