FRA1 mediates the activation of keratinocytes: Implications for the development of psoriatic plaques

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Zolotarenko, Alena¹  Chekalin, Evgeny¹  Piruzian, Eleonora¹  Bruskin, Sergey¹ 

[1] Russian Acad Sci, Vavilov Inst Gen Genet, Lab Funct Genom, Moscow, Russia

关键词: FRA1;    Keratinocytes;    EMT;    Inflammation;    Psoriasis;    Wound healing;   

DOI  :  10.1016/j.bbadis.2018.09.016

来源: Elsevier

【 摘 要 】

In this study we investigated the role of FRA1, a transcription factor from the AP-1 family, in the regulation of keratinocyte characteristics important for the development of psoriatic plaques. FRA1 is characterized by elevated expression in the skin of psoriasis patients, thus leading us to predict it to be one of the major regulators of keratinocyte phenotype during the development of psoriatic lesions. Pathway analysis of RNAseq data allowed us to identify FRA1-mediated signaling cascades leading to the manifestation of the most prominent skin characteristics of the disease: the development of inflammation, epithelial-mesenchymal transition, activation of metalloproteases, and keratinocyte proliferation and migration. We have confirmed that FRA1-overexpressing keratinocytes produce elevated amounts of proinflammatory cytokines and active matrix metalloproteases, leading to the induction of the autoinflammatory loop and paracrine activation in neighbor cells. Therefore, the elevated expression of FRA1 and its altered transcriptional regulation in the skin of patients with psoriasis is an important driving factor in the development of psoriatic plaques.

【 授权许可】

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