Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors expressed in the skin. Three PPAR isotypes, α (NRC1C1), β or δ (NRC1C2) and γ (NRC1C3), have been identified. After activation through ligand binding, PPARs heterodimerize with the 9-cis-retinoic acid receptor (RXR), another nuclear hormone receptor, to bind to specific PPAR-responsive elements in regulatory regions of target genes mainly involved in organogenesis, cell proliferation, cell differentiation, inflammation and metabolism of lipids or carbohydrates. Endogenous PPAR ligands are fatty acids and fatty acid metabolites. In past years, much emphasis has been given to PPARα and γ in skin diseases. PPARβ/δ is the least studied PPAR family member in the skin despite its key role in several important pathways regulating inflammation, keratinocyte proliferation and differentiation, metabolism and the oxidative stress response. This review focuses on the role of PPARβ/δ in keratinocytes and its involvement in psoriasis and atopic dermatitis. Moreover, the relevance of targeting PPARβ/δ to alleviate skin inflammation is discussed.
Highlights
This includes genes involved in fatty acid oxidation (very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL), acyl-CoA oxidase 1 (ACOX1), acetyl-CoA acyltransferase 2 (ACAA2), catalase (CAT), enoyl-CoA hydratase 1 (ECH1), pyruvate dehydrogenase kinase 4 (PDK4), solute carrier family 25 member 20 (SLC25A20), Niemann-Pick C1-like protein 1 (NPC1L1), thiolase B, CPT1A)) or other aspects of lipid metabolism (angiopoietin Like 4 (ANGPTL4), fatty acid binding proteins 3-5 (FABP3-5), perilipin 2 (PLIN2), adipocyte protein 2)
Peroxisomal β-oxidation is upregulated when compared to that of healthy mice, with marked increases in the mRNA, protein and activity levels of ACOX1 [38], a well-known PPARδ downstream target [89,90]. This profile has been observed in another mouse model of lesional atopic dermatitis, i.e., mice topically treated with MC903 [38]
Much of the initial research was focused on PPARα and PPARγ, leaving large gaps in our knowledge of the role of PPARδ in the skin and especially in KCs
Summary
Citation: Blunder, S.; Pavel, P.; Abstract: Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors expressed in the skin. Three PPAR isotypes, α (NRC1C1), β or δ (NRC1C2) and γ (NRC1C3), have been identified. After activation through ligand binding, PPARs heterodimerize with the 9-cis-retinoic acid receptor (RXR), another nuclear hormone receptor, to bind to specific PPAR-responsive elements in regulatory regions of target genes mainly involved in organogenesis, cell proliferation, cell differentiation, inflammation and metabolism of lipids or carbohydrates. Endogenous PPAR ligands are fatty acids and fatty acid metabolites. In past years, much emphasis has been given to PPARα and γ in skin diseases. PPARβ/δ is the least studied PPAR family member in the skin despite its key role in several important pathways regulating inflammation, keratinocyte proliferation and differentiation, metabolism and the oxidative stress response. This review focuses on the role of PPARβ/δ in keratinocytes and its involvement in psoriasis and atopic dermatitis. Moreover, the relevance of targeting PPARβ/δ to alleviate skin inflammation is discussed. Minzaghi, D.; Dubrac, S. PPARdelta in Affected Atopic Dermatitis and Keywords: PPAR; atopic dermatitis; psoriasis; metabolic reprograming; glucose; fatty acids Psoriasis: A Possible Role in Metabolic Reprograming. Int. J. Mol. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Licensee MDPI, Basel, Switzerland. 4.0/).
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