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

Aniko Dozsa, Balazs Dezso, Balazs I. Toth, Attila Bacsi, Szilard Poliska, Emanuela Camera, Mauro Picardo, Christos C. Zouboulis, Tamás Bíró, Gerd Schmitz, Gerhard Liebisch, Ralph Rühl, Eva Remenyik, Laszlo Nagy

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)910-920
Number of pages11
JournalJournal of Investigative Dermatology
Volume134
Issue number4
DOIs
Publication statusPublished - Apr 2014

Fingerprint

PPAR gamma
Arachidonic Acid
Sebaceous Glands
Lipids
Arachidonic Acids
Cells
Angiopoietins
Fluorometry
Biosynthesis
Metabolites
Lipid Metabolism
Adenoma
Mass spectrometry
Real-Time Polymerase Chain Reaction
Mass Spectrometry
Phospholipids
Proteins
Lasers
Transcription Factors
Genes

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

PPARγ-mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes. / Dozsa, Aniko; Dezso, Balazs; Toth, Balazs I.; Bacsi, Attila; Poliska, Szilard; Camera, Emanuela; Picardo, Mauro; Zouboulis, Christos C.; Bíró, Tamás; Schmitz, Gerd; Liebisch, Gerhard; Rühl, Ralph; Remenyik, Eva; Nagy, Laszlo.

In: Journal of Investigative Dermatology, Vol. 134, No. 4, 04.2014, p. 910-920.

Research output: Contribution to journalArticle

Dozsa, Aniko ; Dezso, Balazs ; Toth, Balazs I. ; Bacsi, Attila ; Poliska, Szilard ; Camera, Emanuela ; Picardo, Mauro ; Zouboulis, Christos C. ; Bíró, Tamás ; Schmitz, Gerd ; Liebisch, Gerhard ; Rühl, Ralph ; Remenyik, Eva ; Nagy, Laszlo. / PPARγ-mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes. In: Journal of Investigative Dermatology. 2014 ; Vol. 134, No. 4. pp. 910-920.
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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.",
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AU - Bacsi, Attila

AU - Poliska, Szilard

AU - Camera, Emanuela

AU - Picardo, Mauro

AU - Zouboulis, Christos C.

AU - Bíró, Tamás

AU - Schmitz, Gerd

AU - Liebisch, Gerhard

AU - Rühl, Ralph

AU - Remenyik, Eva

AU - Nagy, Laszlo

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