TY - JOUR
T1 - PPARγ-mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes
AU - Dozsa, Aniko
AU - Dezso, Balazs
AU - Toth, Balazs I.
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
N1 - Funding Information:
The excellent technical assistance of Ibolya Fürtös, Mária Bessenyei, Erika Marton, Katalin Csontos is acknowledged. LN is supported by a grant from the Hungarian Scientific Research Fund (OTKA K100196) and TÁMOP-4.2.2.A-11/1/KONV-2012-0023 implemented through the New Hungary Development Plan, co-financed by the European Social Fund and the European Regional Development Fund. TB is supported by OTKA K101761 and TÁMOP-4.2.2.A-11/1/KONV-2012-0025. EC and MP are supported by the Italian Ministry of Health through the grant RF-2010-2316435.
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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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U2 - 10.1038/jid.2013.413
DO - 10.1038/jid.2013.413
M3 - Article
C2 - 24129064
AN - SCOPUS:84897883565
SN - 0022-202X
VL - 134
SP - 910
EP - 920
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -