High-throughput transcriptome and pathogenesis analysis of clinical psoriasis

J Dermatol Sci. 2020 May;98(2):109-118. doi: 10.1016/j.jdermsci.2020.03.006. Epub 2020 Apr 10.

Abstract

Background: Previous psoriasis studies have mostly focused on skin-related immunology, but the exact mechanisms remain elusive. Clinical evidence, such as higher morbidity among obese individuals and emotional factors, indicate that psoriasis is a complex systemic disease. High-throughput transcriptome analysis provides an effective method to comprehensively assess the disease.

Objective: The present study is aiming to understand transcriptome changes of clinical psoriasis skins and comprehensively assess the diseases using pathways analysis.

Methods: We performed transcriptome sequence of clinical psoriatic samples. Biological pathway analyses were conducted using differentially expressed RNAs, as well as identified competing endogenous RNAs (ceRNAs). qRT-PCR and histological immunofluorescence staining was conducted to verify the differentially expressed RNAs (DE_RNAs) and the three important enriched biological pathways.

Results: Numerous DE_RNAs were identified between psoriasis patients and healthy people. Functional analysis indicated PPAR-fatty acids metabolism pathways, neural-hormone regulations, circadian entrainment were the three mostly appeared pathways. For PPAR-fatty acids metabolism pathways, the expression of seven randomly selected genes, including ACSBG1, ACOT2), CYP27A1, ELOVL3, FABP7, FADS2 and PPARG were all significantly decreased in psoriasis lesions. For neural-hormone regulation pathways, the expression of CFL1, EPHA2, HRAS were all significantly upregulated in psoriasis lesions. While the expression of four randomly selected genes from circadian entrainment pathways, including CRY2, PER3, NR1D1 and RORC were all significantly downregulated. Histological immunofluorescence staining of FADS2, EPHA2 and CRY2 were consistent with their genes' expressions.

Conclusion: Our results revealed transcriptome changes of psoriasis, and indicated three important pathways involved in psoriasis, including PPAR-fatty acids metabolism pathways, neural-hormone regulations, circadian entrainment.

Keywords: Circadian entrainment; High-throughput transcriptome; Neural-hormone regulation; PPAR-fatty acid metabolism; Psoriasis.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Case-Control Studies
  • Circadian Clocks / genetics
  • Computational Biology
  • Fatty Acids / metabolism
  • Female
  • Gene Regulatory Networks*
  • Healthy Volunteers
  • Humans
  • Lipid Metabolism / genetics
  • Male
  • Middle Aged
  • PPAR gamma / metabolism
  • Psoriasis / etiology*
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • RNA-Seq
  • Signal Transduction / genetics*
  • Skin / pathology*
  • Transcriptome*
  • Young Adult

Substances

  • Fatty Acids
  • PPAR gamma
  • PPARG protein, human