Differential Expression of Proteins Involved in Skin Barrier Maintenance and Vitamin D Metabolism in Atopic Dermatitis: A Cross-Sectional, Exploratory Study

Int J Mol Sci. 2024 Dec 30;26(1):211. doi: 10.3390/ijms26010211.

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by proteins involved in skin barrier maintenance and vitamin D metabolism. Using an intra-patient design, this study compared protein expression in intra-lesional (IL) and peri-lesional (PL) skin biopsies from AD patients and examined associations between protein levels, vitamin D status, and clinical features. Forty-four biopsies from twenty-two AD patients were analyzed using antibody microarrays targeting twelve proteins. IL samples had significantly higher total protein levels than PL samples, with a mean difference of 77.7% (p < 0.001). Several proteins, including cathelicidin, cingulin, occludin, filaggrin, and the vitamin D receptor, were upregulated in IL samples. Patients with vitamin D levels below 30 ng/mL showed higher expression of CYP24A (p = 0.054), alpha-catenin (p = 0.043), and haptoglobin (p = 0.033). Increased EASI scores (≥16) were associated with elevated expression of CYP24A (p = 0.024), CYP27B (p = 0.044), filaggrin (p = 0.027), occludin (p = 0.049), and claudin-1 (p = 0.052). Multivariate regression analysis identified significant correlations between protein expression, skin prick test positivity, and low vitamin D levels. These findings suggest that proteins related to epithelial barrier function and vitamin D metabolism are highly upregulated in IL skin regions, offering potential therapeutic targets for improving both skin barrier function and overall disease severity in AD patients.

Keywords: atopic dermatitis; protein expression; skin barrier maintenance; vitamin D receptor.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Adult
  • Antimicrobial Cationic Peptides / metabolism
  • Cathelicidins* / metabolism
  • Cross-Sectional Studies
  • Dermatitis, Atopic* / metabolism
  • Dermatitis, Atopic* / pathology
  • Female
  • Filaggrin Proteins* / metabolism
  • Haptoglobins / metabolism
  • Humans
  • Intermediate Filament Proteins / metabolism
  • Male
  • Middle Aged
  • Occludin / metabolism
  • Skin* / metabolism
  • Skin* / pathology
  • Vitamin D* / blood
  • Vitamin D* / metabolism
  • Vitamin D-Binding Protein
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamin D3 24-Hydroxylase / metabolism
  • Young Adult

Substances

  • Filaggrin Proteins
  • Vitamin D
  • FLG protein, human
  • Cathelicidins
  • Vitamin D3 24-Hydroxylase
  • Occludin
  • Antimicrobial Cationic Peptides
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • OCLN protein, human
  • GC protein, human
  • Haptoglobins
  • Intermediate Filament Proteins
  • CYP27B1 protein, human
  • Vitamin D-Binding Protein