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Decreased retinoid concentration and retinoid signalling pathways in human atopic dermatitis

Johanna Mihály1, Anat Gamlieli, Margitta Worm

  • 1Laboratory of Nutritional Bioactivation and Bioanalysis, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.

Experimental Dermatology
|March 18, 2011
PubMed

Insights

Retinoid signaling pathways and concentrations are significantly reduced in both affected and non-affected skin of atopic dermatitis (AD) patients, indicating an intrinsic skin defect. This impacts retinoid transport, synthesis, and signaling in AD.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Biochemistry

Background:

  • Atopic dermatitis (AD) is a prevalent inflammatory skin condition.
  • Retinoids play a crucial role in regulating skin homeostasis, including epidermal differentiation and inflammation.
  • Dysregulation of retinoid pathways is implicated in various skin diseases.

Purpose of the Study:

  • To investigate retinoid signaling pathways and retinoid concentration profiles in the skin of patients with atopic dermatitis.
  • To compare gene expression of retinoid-related molecules and retinoid levels in healthy skin versus atopic dermatitis skin (affected and non-affected).

Main Methods:

  • Human skin biopsies from healthy volunteers and AD patients (affected and non-affected skin) were analyzed.
  • Quantitative Reverse Transcription Polymerase Chain Reaction (QRT-PCR) was used to assess gene expression of retinoid receptors, binding proteins, and metabolizing enzymes.
  • High-performance liquid chromatography-mass spectrometry-mass spectrometry was employed to measure retinoid concentrations in serum and skin.

Main Results:

  • Gene expression of retinoid receptor-regulated pathways was significantly decreased in both affected (AS) and non-affected skin (NAS) of AD patients compared to healthy subjects (HS).
  • Key enzymes like CYP26A1, transglutaminase 2, and retinoic acid receptor responder 1 showed reduced expression in AS and NAS.
  • The primary retinoic acid synthesizing enzyme, retinal dehydrogenase 1, was significantly downregulated in AD skin.
  • While serum retinoid levels were comparable, affected and non-affected AD skin exhibited significantly reduced concentrations of all-trans retinoic acid (ATRA) and retinol (ROL) compared to healthy skin.

Conclusions:

  • Retinoid transport, synthesis, concentrations, and signaling are markedly diminished in the skin of AD patients, affecting both lesional and non-lesional areas.
  • These findings suggest a generalized, intrinsic impairment of the skin retinoid signaling pathway in individuals with atopic dermatitis.
  • This intrinsic defect may contribute to the pathogenesis and characteristic features of atopic dermatitis.

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