Peroxisome Proliferator-Activated Receptor (PPAR)-[beta]/[delta] Stimulates Differentiation and Lipid Accumulation in Keratinocytes
Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier h...
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| Veröffentlicht in: | Journal of investigative dermatology 2004-04, Vol.122 (4), p.971 |
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| creator | Schmuth, Matthias Haqq, Christopher M Cairns, William J Holder, Julie C Dorsam, Sheri Chang, Sandra Lau, Peggy Fowler, Ashley J Chuang, Gary Moser, Arthur H Brown, Barbara E Mao-Qiang, Man Uchida, Yoshikazu Schoonjans, Kristina Auwerx, Johan Chambon, P |
| description | Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes. |
| doi_str_mv | 10.1111/j.0022-202X.2004.22412.x |
| format | Article |
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Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.</description><identifier>ISSN: 0022-202X</identifier><identifier>EISSN: 1523-1747</identifier><identifier>DOI: 10.1111/j.0022-202X.2004.22412.x</identifier><language>eng</language><publisher>London: Elsevier Limited</publisher><ispartof>Journal of investigative dermatology, 2004-04, Vol.122 (4), p.971</ispartof><rights>Copyright Nature Publishing Group Apr 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210376305?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,64385,64389,72469</link.rule.ids></links><search><creatorcontrib>Schmuth, Matthias</creatorcontrib><creatorcontrib>Haqq, Christopher M</creatorcontrib><creatorcontrib>Cairns, William J</creatorcontrib><creatorcontrib>Holder, Julie C</creatorcontrib><creatorcontrib>Dorsam, Sheri</creatorcontrib><creatorcontrib>Chang, Sandra</creatorcontrib><creatorcontrib>Lau, Peggy</creatorcontrib><creatorcontrib>Fowler, Ashley J</creatorcontrib><creatorcontrib>Chuang, Gary</creatorcontrib><creatorcontrib>Moser, Arthur H</creatorcontrib><creatorcontrib>Brown, Barbara E</creatorcontrib><creatorcontrib>Mao-Qiang, Man</creatorcontrib><creatorcontrib>Uchida, Yoshikazu</creatorcontrib><creatorcontrib>Schoonjans, Kristina</creatorcontrib><creatorcontrib>Auwerx, Johan</creatorcontrib><creatorcontrib>Chambon, P</creatorcontrib><title>Peroxisome Proliferator-Activated Receptor (PPAR)-[beta]/[delta] Stimulates Differentiation and Lipid Accumulation in Keratinocytes</title><title>Journal of investigative dermatology</title><description>Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.</description><issn>0022-202X</issn><issn>1523-1747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNjU1LxDAYhIMoWFf_Q_Ckh2STtN16LX6woIey60FYZInpW3hLN6lJKuvZP25WxLNzGZh5hiGESsFl0rznQijFlFAvXAlRcKUKqfj-iGSyVDmTVVEdk-wPOiVnIfRCyEVR3mTkqwHv9hjcDmjj3YAdeB2dZ7WJ-KEjtHQFBsYU0aumqVfXbPMGUb_ONy0Myek64m4aEhnoHXZpDjaijugs1balTzhiS2tjph_qEKOlj4cXtM58pt05Oen0EODi12fk8uH--XbJRu_eJwhx27vJ21RtlRR5tchFmf8L-gaCI1n4</recordid><startdate>20040401</startdate><enddate>20040401</enddate><creator>Schmuth, Matthias</creator><creator>Haqq, Christopher M</creator><creator>Cairns, William J</creator><creator>Holder, Julie C</creator><creator>Dorsam, Sheri</creator><creator>Chang, Sandra</creator><creator>Lau, Peggy</creator><creator>Fowler, Ashley J</creator><creator>Chuang, Gary</creator><creator>Moser, Arthur H</creator><creator>Brown, Barbara E</creator><creator>Mao-Qiang, Man</creator><creator>Uchida, Yoshikazu</creator><creator>Schoonjans, Kristina</creator><creator>Auwerx, Johan</creator><creator>Chambon, P</creator><general>Elsevier Limited</general><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope></search><sort><creationdate>20040401</creationdate><title>Peroxisome Proliferator-Activated Receptor (PPAR)-[beta]/[delta] Stimulates Differentiation and Lipid Accumulation in Keratinocytes</title><author>Schmuth, Matthias ; 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Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. 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| title | Peroxisome Proliferator-Activated Receptor (PPAR)-[beta]/[delta] Stimulates Differentiation and Lipid Accumulation in Keratinocytes |
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