Dyslipidemia initiates keratinocytes proliferation through upregulation of lncRNA NEAT in psoriasis patients

Mol Biol Rep. 2023 Sep;50(9):7597-7604. doi: 10.1007/s11033-023-08527-w. Epub 2023 Aug 2.

Abstract

Background: Psoriasis is a chronic inflammatory immune-mediated and hyper proliferative skin disorder that has underlying genetic factors. Psoriasis can result from interaction of cytokines between keratinocytes and T-lymphocytes. NEAT is a lncRNA involved in immune modulation and has been previously studied in cancers. This study aims to clarify the unprecedented role of NEAT in psoriasis pathogenesis.

Methods: The study was conducted on 50 healthy control subjects and 50 psoriasis patients. Blood samples from all participants were collected for analysis of their lipid profile. qRT-PCR was done for lncRNA NEAT, TNF-α, VEGF genes expression. The levels of ROS and caspase-3 were estimated by ELISA. ROC analysis was done to detect the diagnostic value of lncRNA NEAT gene expression.

Results: Dyslipidemia is more prevalent among psoriasis patients. A significant up regulation in lncRNA NEAT, TNF-α, VEGF genes expression (p value˂0.001) in psoriasis patients in addition to significant increase in ROS and caspase-3 levels (p value˂0.001) in compare to controls. Additionally, a positive significant correlation between TNF-α, ROS, NEAT, caspase-3 and dyslipidemia. NEAT had an area under the curve (AUC) of 0.931 (95% CI 0.844-0.978, p < 0.001).

Conclusion: Dyslipidemia is an initiating signal in psoriasis pathogenesis that creates a state of chronic inflammation and oxidative stress. This state induces keratinocytes proliferation and release of NEAT with subsequent caspase-3 activation to counteract the proliferating cells. NEAT could be considered as a good diagnostic biomarker for psoriasis.

Keywords: Caspase-3; NEAT; Psoriasis; ROS; TNF-α; VEGF.

MeSH terms

  • Caspase 3 / metabolism
  • Cell Proliferation / genetics
  • Dyslipidemias* / metabolism
  • Humans
  • Inflammation / metabolism
  • Keratinocytes / metabolism
  • Psoriasis* / genetics
  • Psoriasis* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Caspase 3
  • RNA, Long Noncoding
  • Tumor Necrosis Factor-alpha
  • Reactive Oxygen Species
  • Vascular Endothelial Growth Factor A