期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 122, 期 4, 页码 971-983出版社
ELSEVIER SCIENCE INC
DOI: 10.1111/j.0022-202X.2004.22412.x
关键词
barrier function; fasting; lipid; nuclear hormone receptor; stratum corneum
类别
资金
- Austrian Science Fund FWF [P 16990] Funding Source: Medline
- NIAMS NIH HHS [AR39448] Funding Source: Medline
- NICHD NIH HHS [HD29706] Funding Source: Medline
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 (GW501516) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation. In contrast to PPAR-alpha activation, PPAR-beta/delta in vivo did not display anti-proliferative or proapoptotic 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.
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