Dynamin-related protein 1 expression correlates with psoriasis disease severity and regulates keratinocyte function

Eur J Dermatol. 2020 Aug 1;30(4):329-337. doi: 10.1684/ejd.2020.3849.

Abstract

Background: The pathogenesis of psoriasis is still not fully understood. Dynamin-related protein 1 (Drp1) regulates mitochondrial fission and is implicated in various inflammatory conditions, but research regarding Drp1 in the skin is scarce.

Objectives: To examine Drp1 expression in psoriasis vulgaris lesional skin and the effect of Drp1 expression on keratinocyte proliferation and inflammatory mediator release in vitro.

Materials and methods: Skin biopsies were collected, and the expression of Drp1 and TNF-α was investigated in the skin. Serum TNF-α level was also examined. The effect of Drp1 on keratinocyte proliferation and inflammatory mediator release was evaluated in HaCaT cells following Drp1 transfection. The effect of TNF-α on Drp1 expression was also studied in HaCaT cells.

Results: Drp1 expression was significantly increased and positively correlated with PASI score and TNF-α expression in skin. In HaCaT cells, Drp1 transfection altered cellular ATP and proliferation, induced G2/M arrest, and affected inflammatory mediator (TNF-α, IL-6 and CXCL8) release. Moreover, TNF-α induced Drp1 expression and recovered cellular ATP content and mediator release.

Conclusion: Drp1 is significantly elevated in psoriasis vulgaris skin and positively correlates with disease severity, moreover, in vitro, Drp1 regulates keratinocyte function.

Keywords: TNF-α; dynamin-related protein 1; inflammation; keratinocytes; mitochondria; psoriasis vulgaris.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Division
  • Cell Proliferation*
  • Dynamins / genetics
  • Dynamins / metabolism*
  • G2 Phase Cell Cycle Checkpoints / physiology
  • HaCaT Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Keratinocytes / physiology*
  • Mitochondrial Dynamics
  • Psoriasis / metabolism*
  • Psoriasis / physiopathology*
  • Severity of Illness Index
  • Skin / metabolism*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Inflammation Mediators
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Adenosine Triphosphate
  • DNM1L protein, human
  • Dynamins