PPAR gamma-Mediated and Arachidonic Acid-Dependent Signaling Is Involved in Differentiation and Lipid Production of Human Sebocytes

Dozsa, Aniko and Dezso, Balazs and Toth, Balazs I. and Bacsi, Attila and Poliska, Szilard and Camera, Emanuela and Picardo, Mauro and Zouboulis, Christos C. and Biro, Tamas and Schmitz, Gerd and Liebisch, Gerhard and Ruehl, Ralph and Remenyik, Eva and Nagy, Laszlo (2014) PPAR gamma-Mediated and Arachidonic Acid-Dependent Signaling Is Involved in Differentiation and Lipid Production of Human Sebocytes. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 134 (4). pp. 910-920. ISSN 0022-202X, 1523-1747

Full text not available from this repository. (Request a copy)

Abstract

The transcriptional basis of sebocyte differentiation and lipid production is mostly unclear. Peroxisome proliferator-activated receptor gamma (PPAR gamma), a lipid-activated transcription factor, has been implicated in differentiation and lipid metabolism of various cell types. Here, we show that PPAR gamma 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 PPAR gamma and its target genes, ADRP (adipose differentiation-related protein) and PGAR (PPAR gamma angiopoietin-related protein), are expressed in sebocytes and show association with their level of differentiation. Also, PPAR gamma 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 PPAR gamma signaling pathways, which in turn modulate phospholipid biosynthesis and induce neutral lipid synthesis. Collectively, our findings highlight the importance of endogenous ligand-activated PPAR gamma signaling in human sebocyte biology and suggest that PPAR gamma might be a promising candidate for the clinical management of SG disorders.

Item Type: Article
Uncontrolled Keywords: PROLIFERATOR-ACTIVATED-RECEPTOR; TANDEM MASS-SPECTROMETRY; HIGH-THROUGHPUT QUANTIFICATION; PEROXISOME-PROLIFERATOR; DENDRITIC CELLS; TRANSCRIPTION FACTORS; PROSTAGLANDIN E-2; SEBACEOUS GLANDS; RETINOIC ACID; ESI-MS/MS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 Nov 2019 11:56
Last Modified: 15 Nov 2019 11:56
URI: https://pred.uni-regensburg.de/id/eprint/10420

Actions (login required)

View Item View Item