ELF3 promotes the development of psoriasis through transcriptional up-regulation of ADAM8 expression.

Abstract

Psoriasis is a systemic inflammatory disorder that has a significant impact on the quality of life of patients. E74-like factor 3 (ELF3) is a common transcriptional mediator of inflammation, but the effect of ELF3 on psoriasis development and severity is poorly understood. In this study, we first collected clinical normal skin tissues and skin tissues of psoriasis patients to detect the mRNA and protein levels of ELF3 and found that ELF3 was highly expressed in psoriasis skin tissues. We further used the imiquimod (IMQ)-induced mice model to mimic the phenotypic changes of human psoriasis in vivo, which are manifested as scaling, epidermal hyperplasia, and erythema formation, but knockdown of ELF3 resulted in suppression of these phenomena. In addition, downregulation of ELF3 expression inhibited neoangiogenesis and inflammatory cell infiltration. On this basis, we further found that ELF3 promotes the proliferation, angiogenesis, and inflammatory response of human keratinocyte HaCaT in vitro. Mechanistically, we found that ELF3 transcriptionally activated the activity of the downstream factor ADAM metallopeptidase domain 8 (ADAM8) by dual luciferase assays, thereby exacerbating the severity of psoriasis. We concluded that ELF3 is a key target for exacerbating psoriasis pathologic manifestations and promoting disease progression.