We show here that the α, β, and γ isotypes of peroxisome proliferator–activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfollicular epithelium after birth. Interestingly, PPARα and β expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing. Using PPARα, β, and γ mutant mice, we demonstrate that PPARα and β are important for the rapid epithelialization of a skin wound and that each of them plays a specific role in this process. PPARα is mainly involved in the early inflammation phase of the healing, whereas PPARβ is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPARβ mutant primary keratinocytes show impaired adhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPARα and β in adult mouse epidermal repair.
Oxidative stress of human skin fibroblasts by treatment with ultraviolet A (UVA) radiation has been shown to lead to an increase in levels of the heme catabolizing enzyme heme oxygenase 1 [heme, hydrogen-donor:oxygen oxidoreductase (a-methene-oxidizing, hydroxylating), EC 1.14.99.3] and the iron storage protein ferritin. Here we show that human skin fibroblasts, preirradiated with UVA, sustain less membrane damage during a subsequent exposure to UVA radiation than cells that had not been preirradiated. Pretreating cells with heme oxygenase 1 antsense oligonucleotide inhibited the irradiationdependent induction of both the heme oxygenase 1 enzyme and feritin and abolished the protective effect of preirradiation. Inhibition of the UVA preirradiation-dependent increase in femtin, but not heme oxygenase, with desferrioxamine also abolished the protection. This identifies heme oxygenase 1 as a crucial enzymatic intermediate in an oxidant stress-inducible antioxidant defense mechanis, involving ferritin, in human skin fibroblasts.Expression of the heme oxygenase 1 gene is enhanced by oxidative stress (1-6) including UVA radiation (320-380 nm) (7-9), a major component of sunlight. We have recently demonstrated that induction of the heme oxygenase enzyme [heme, hydrogen-donor:oxygen oxidoreductase (a-metheneoxidizing, hydroxylating), EC 1.14.99.3] by UVA irradiation of cultured human skin fibroblasts leads to an increase in ferritin (10). Ferritin constitutes the major storage site for nonmetabolized intracellular iron and therefore plays a critical role in regulating the availability of iron to catalyze such harmful reactions as the peroxidation oflipids and the Fenton reaction producing hydroxyl radicals. Recent studies have implicated intracellular ferritin in the protection of rat kidney (11) and cultured aortic endothelial cells (12) from oxidantinduced damage. This study was undertaken to determine whether a heme oxygenase-dependent increase in ferritin levels leads to an adaptive response in human skin fibroblasts. MATERIALS AND METHODS 2607The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
PPARs are members of the nuclear hormone receptor superfamily and are primarily involved in lipid metabolism. The expression patterns of all 3 PPAR isotypes in 22 adult rat organs were analyzed by a quantitative ribonuclease protection assay. The data obtained allowed comparison of the expression of each isotype to the others and provided new insight into the less studied PPAR beta (NR1C2) expression and function. This isotype shows a ubiquitous expression pattern and is the most abundant of the three PPARs in all analyzed tissues except adipose tissue. Its expression is especially high in the digestive tract, in addition to kidney, heart, diaphragm, and esophagus. After an overnight fast, PPAR beta mRNA levels are dramatically down-regulated in liver and kidney by up to 80% and are rapidly restored to control levels upon refeeding. This tight nutritional regulation is independent of the circulating glucocorticoid levels and the presence of PPAR alpha, whose activity is markedly up-regulated in the liver and small intestine during fasting. Finally, PPAR gamma 2 mRNA levels are decreased by 50% during fasting in both white and brown adipose tissue. In conclusion, fasting can strongly influence PPAR expression, but in only a few selected tissues.
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate the expression of many genes involved in lipid metabolism. The biological roles of PPAR␣ and PPAR␥ are relatively well understood, but little is known about the function of PPAR. To address this question, and because PPAR is expressed to a high level in the developing brain, we used reaggregated brain cell cultures prepared from dissociated fetal rat telencephalon as experimental model. In these primary cultures, the fetal cells initially form random aggregates, which progressively acquire a tissue-specific pattern resembling that of the brain. PPARs are differentially expressed in these aggregates, with PPAR being the prevalent isotype. PPAR␣ is present at a very low level, and PPAR␥ is absent. Cell typespecific expression analyses revealed that PPAR is ubiquitous and most abundant in some neurons, whereas PPAR␣ is predominantly astrocytic. We chose acyl-CoA synthetases (ACSs) 1, 2, and 3 as potential target genes of PPAR and first analyzed their temporal and cell type-specific pattern. This analysis indicated that ACS2 and PPAR mRNAs have overlapping expression patterns, thus designating the ACS2 gene as a putative target of PPAR. Using a selective PPAR activator, we found that the ACS2 gene is transcriptionally regulated by PPAR, demonstrating a role for PPAR in brain lipid metabolism.Peroxisome proliferator-activated receptors (PPARs) 1 are members of the nuclear hormone receptor superfamily. Three PPAR isotypes, ␣,  (also called ␦, FAAR, and NUC1), and ␥, have been cloned from Xenopus, rodents, and human. PPARs regulate gene expression by binding as heterodimers with retinoid X receptors to peroxisome proliferator response elements in the promoter of genes involved in lipid metabolism (1-3).The biological roles of PPAR␣ and PPAR␥ are relatively well understood, not least because specific ligands for these isotypes have been identified (4). PPAR␣ regulates genes involved in peroxisomal and mitochondrial -oxidation as well as lipoprotein metabolism (2, 5). PPAR␣ also suppresses apoptosis in cultured rat hepatocytes (6) and reduces inflammatory responses (7, 8). PPAR␥ stimulates adipogenesis, enhances insulin sensitivity, and is involved in cell cycle control and regulation of tumor growth (9 -13).In contrast, the functions of PPAR are poorly understood, due partly to its ubiquitous expression and the lack of a selective ligand. The objective of this study was to start unraveling PPAR functions using an experimental model that is easy to manipulate and that expresses high levels of PPAR compared with PPAR␣ and PPAR␥. The nervous system seemed an appropriate target for this, as PPAR is abundantly expressed in brain from embryogenesis to adulthood, whereas PPAR␣ and PPAR␥ are barely detectable (14 -17). The brain is the organ with the highest lipid concentration in the body, second only to adipose tissue. Brain lipids serve primarily in modifying the fluidity, structure, and functions of the membrane...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.