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J Invest Dermatol. 2014 Apr;134(4):910-920. doi: 10.1038/jid.2013.413. Epub 2013 Oct 15.

PPARγ-mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes.

Author information

1
Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; Department of Dermatology, Health Care Center, Miskolc, Hungary.
2
Department of Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
3
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.
4
Department of Immunology, University of Debrecen, Debrecen, Hungary.
5
Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
6
Laboratory of Cutaneous Physiopathology and Integrated Center for Metabolomics Research, Institute of Dermatology San Gallicano (IRCCS), Rome, Italy.
7
Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
8
Departments of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
9
Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
10
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.

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.

PMID:
24129064
DOI:
10.1038/jid.2013.413
[Indexed for MEDLINE]
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