Korean J Dermatol.  2022 Dec;60(10):640-646.

Effect of Activating Transcription Factor 3 on Inflammatory Response and Differentiation of Keratinocytes

Affiliations
  • 1Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea

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.

Keyword

Activating transcription factor 3; Differentiation; Inflammation; Keratinocytes; Psoriasis
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