title: Decreased retinoid concentration and retinoid signalling pathways in human atopic dermatitis.
abstract: Atopic dermatitis (AD) is one of the most common skin diseases. Various features present in AD like inflammation, reduced apoptosis, altered epidermal differentiation and hyperproliferation as well as permeability dysfunction are also regulated by retinoids. The aim of our study is to identify the retinoid signalling pathways and retinoid concentration profiles in AD skin. Human skin biopsies were obtained from healthy volunteers (HS) (n=6) and patients with AD (n=6), with both affected (AS) and non-affected (NAS) skin. The gene expression of retinoid receptors, retinoid-binding proteins and retinoid-metabolizing enzymes was investigated by QRT-PCR. Retinoid concentrations in serum and skin were measured via high performance liquid chromatography mass spectrometry-mass spectrometry. Our results show that the target gene expression of retinoid receptor regulated pathways is significantly decreased in AS and NAS of patients with AD. CYP26A1, transglutaminase 2 and retinoic acid receptor responder 1 decreased in NAS and AS in comparison with HS. The main retinoic acid synthesizing enzyme, retinal dehydrogenase 1, was significantly lower expressed in NAS (0.1%) and AS (1%) in patients with AD. Analysis of retinoid concentration in serum and skin showed comparable all-trans retinoic acid (ATRA) and retinol (ROL) concentrations from AD and healthy serum, but strongly reduced ATRA and ROL concentrations in affected and non-affected skin in comparison with healthy skin. Our data indicate that retinoid transport, synthesis, concentrations and signalling are strongly decreased in the affected but also in non-affected skin of patients with AD suggesting a general intrinsic influence on skin retinoid signalling pathway in patients with AD.
authors.affiliation: Laboratory of Nutritional Bioactivation and Bioanalysis, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mihály
authors.forename: Anat
authors.initials: A
authors.lastname: Gamlieli
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
authors.forename: Ralph
authors.initials: R
authors.lastname: Rühl
mesh_terms: D000293:Adolescent; D000328:Adult; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D012176:Retinoids / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology / Q000378:metabolism*; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000097:blood / Q000378:metabolism; D014801:Vitamin A / Q000097:blood / Q000378:metabolism; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C452562:RARRES1 protein, human; D012333:RNA, Messenger; D012176:Retinoids; D014801:Vitamin A; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D050697:Retinal Dehydrogenase; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins