Transcriptional regulatory network for psoriasis

Authors


  • Author contribution: Xiaonian Lu and Juan Du are joint first authors of this study.
  • Conflict of interest: none.

Correspondence: Jinhua Xu, Ph.D., Department of Dermatology, Huashan Hospital, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China. Email: jinhuaxujhx@hotmail.com

Abstract

Psoriasis is a common, chronic, intractable skin disease that affects approximately 2% of the world's population. Transcriptional regulation is one of the most fundamental processes in psoriasis. However, high-throughput functional analysis of multiple transcription factors and their target genes in psoriasis is still rare. Thus, the objective of our study was to interpret the mechanisms of psoriasis through the regulation network construction using the GSE14905 microarray data. The results showed E2F transcription factor 1 (E2F1), jun proto-oncogene (JUN), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1), signal transducer and activator of transcription 1 (STAT1), STAT3 and SP3 were hinge points in our transcriptome network. Importantly, JUN may regulate activating transcription factor 3 expression to involve cell proliferation process; STAT1 and STAT3 can inhibit tissue inhibitor of metalloproteinases-3 expression to modulate the cell adhesion molecule pathway; NF-κB and E2F1 can downregulate cyclin D1, but upregulate proliferating cell nuclear antigen expression to promote the cell cycle pathway. In addition, the regulation network between transcription factors and pathways revealed that NF-κB1 could promote the Toll-like receptor signaling pathway and that SP3 may inhibit the steroid hormone biosynthesis pathway in psoriasis. This transcriptional regulation analysis may provide a better understanding of molecular mechanism and some potential therapeutic targets in the treatment of human psoriasis.

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