Rh family C glycoprotein contributes to psoriatic inflammation through regulating the dysdifferentiation and cytokine secretion of keratinocytes

J Dermatol Sci. 2024 Apr;114(1):2-12. doi: 10.1016/j.jdermsci.2024.02.007. Epub 2024 Feb 29.

Abstract

Background: Keratinocyte dysdifferentiation and proinflammatory cytokine production play a central role in psoriatic inflammation. According to recent studies, the Rh family C glycoprotein (RHCG) enhances cell proliferation and disrupts cell differentiation. However, the specific role of RHCG psoriasis development remains unclear.

Objective: We here explored the effect of RHCG on keratinocytes under psoriatic inflammation.

Methods: The cell counting kit‑8 assay was conducted to assess proliferation. RHCG protein expression was assessed through western blotting and enzyme-linked immunosorbent assays. The expression of proinflammatory cytokines and differentiation markers was analyzed through a quantitative reverse-transcription polymerase chain reaction.

Results: Both RHCG mRNA and protein levels increased in psoriatic skin. Notably, cultured keratinocytes treated with an M5 cocktail, which mimics psoriatic inflammation, exhibited higher RHCG expression. Furthermore, RHCG overexpression promoted keratinocyte proliferation, accompanied by an increase in the production of interleukin (IL)-1β, IL-6, and IL-8, and tumor necrosis factor-α. RHCG overexpression also resulted in higher expression of keratin 17, a differentiation marker. Conversely, RHCG gene knockdown reduced keratinocyte proliferation and cytokine secretion. RHCG inhibition in cells recovered both keratin 1 and loricrin expression. Additionally, RHCG overexpression facilitated the phosphorylation of nuclear factor-kappa B and extracellular signal-regulated protein kinase signaling pathways. Importantly, when these signaling pathways were inhibited, the effect of RHCG on keratinocytes was attenuated.

Conclusion: These findings support the substantial role of RHCG in psoriatic inflammation development and suggest that RHCG serves as a potential target for psoriasis treatment.

Keywords: Rh family C glycoprotein; differentiation; keratinocyte; proinflammatory factor; psoriasis.

MeSH terms

  • Adult
  • Cell Differentiation*
  • Cell Proliferation*
  • Cells, Cultured
  • Cytokines* / metabolism
  • Female
  • Humans
  • Keratinocytes* / metabolism
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Psoriasis* / immunology
  • Psoriasis* / metabolism
  • Psoriasis* / pathology
  • Signal Transduction
  • Skin / cytology
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology

Substances

  • Cytokines
  • NF-kappa B