title: PPARγ-mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes.
abstract: The transcriptional basis of sebocyte differentiation and lipid production is mostly unclear. Peroxisome proliferator-activated receptor gamma (PPARγ), a lipid-activated transcription factor, has been implicated in differentiation and lipid metabolism of various cell types. Here, we show that PPARγ is differentially expressed in normal and pathological human sebocytes and appears to have roles in their differentiation and lipid production. We used laser-microdissected normal and pathological human sebaceous glands (SGs) and SZ95 cells (immortalized sebocyte cell line) analyzed by real-time quantitative PCR and immunohistochemistry. Lipids were analyzed by quantitative fluorimetry- and mass spectrometry-based approaches. We have observed that PPARγ and its target genes, ADRP (adipose differentiation-related protein) and PGAR (PPARγ angiopoietin-related protein), are expressed in sebocytes and show association with their level of differentiation. Also, PPARγ is present in normal and hyperplastic SG, whereas its expression levels are decreased in SG adenoma and SG carcinoma cells, reflecting a maturation-linked expression pattern. Furthermore, in SZ95 sebocytes, naturally occurring lipids, including arachidonic acid and arachidonic acid keto-metabolites (e.g., 5-KETE (5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid), 12-KETE (12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid)), appear to regulate PPARγ signaling pathways, which in turn modulate phospholipid biosynthesis and induce neutral lipid synthesis. Collectively, our findings highlight the importance of endogenous ligand-activated PPARγ signaling in human sebocyte biology and suggest that PPARγ might be a promising candidate for the clinical management of SG disorders.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; Department of Dermatology, Health Care Center, Miskolc, Hungary.
authors.forename: Aniko
authors.initials: A
authors.lastname: Dozsa
authors.affiliation: Department of Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Dezso
authors.affiliation: DE-MTA "Lendület" Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary.
authors.forename: Balazs I
authors.initials: BI
authors.lastname: Toth
authors.affiliation: Department of Immunology, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Bacsi
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Szilard
authors.initials: S
authors.lastname: Poliska
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center for Metabolomics Research, Institute of Dermatology San Gallicano (IRCCS), Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Camera
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center for Metabolomics Research, Institute of Dermatology San Gallicano (IRCCS), Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
authors.affiliation: Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
authors.forename: Christos C
authors.initials: CC
authors.lastname: Zouboulis
authors.affiliation: DE-MTA "Lendület" Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
authors.affiliation: Departments of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.affiliation: Departments of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Ralph
authors.initials: R
authors.lastname: Rühl
authors.affiliation: Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Remenyik
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; DE-MTA "Lendület" Immunogenomics Research Group, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary. Electronic address: nagyl@med.unideb.hu.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D000070780:Perilipin-2; D012627:Sebaceous Glands / Q000166:cytology* / Q000378:metabolism*; D012629:Sebum / Q000166:cytology*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D008055:Lipids; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D047495:PPAR gamma; D000070780:Perilipin-2; D016718:Arachidonic Acid