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Liver X receptor is a therapeutic target for photoaging and chronological skin aging.
- Source :
-
Molecular endocrinology (Baltimore, Md.) [Mol Endocrinol] 2008 Nov; Vol. 22 (11), pp. 2407-19. Date of Electronic Publication: 2008 Sep 11. - Publication Year :
- 2008
-
Abstract
- Liver X receptors (LXRalpha and -beta) are liposensors that exert their metabolic effects by orchestrating the expression of macrophage genes involved in lipid metabolism and inflammation. LXRs are also expressed in other tissues, including skin, where their natural oxysterol ligands induce keratinocyte differentiation and improve epidermal barrier function. To extend the potential use of LXR ligands to dermatological indications, we explored the possibility of using LXR as a target for skin aging. We demonstrate that LXR signaling is down-regulated in cell-based models of photoaging, i.e. UV-activated keratinocytes and TNFalpha-activated dermal fibroblasts. We show that a synthetic LXR ligand inhibits the expression of cytokines and metalloproteinases in these in vitro models, thus indicating its potential in decreasing cutaneous inflammation associated with the etiology of photoaging. Furthermore, a synthetic LXR ligand induces the expression of differentiation markers, ceramide biosynthesis enzymes, and lipid synthesis and transport genes in keratinocytes. Remarkably, LXRbeta-null mouse skin showed some of the molecular defects that are observed in chronologically aged human skin. Finally, we demonstrate that a synthetic LXR agonist inhibits UV-induced photodamage and skin wrinkle formation in a murine model of photoaging. Therefore, the ability of an LXR ligand to modulate multiple pathways underlying the etiology of skin aging suggests that LXR is a novel target for developing potential therapeutics for photoaging and chronological skin aging indications.
- Subjects :
- Animals
Cell Differentiation
Cells, Cultured
DNA-Binding Proteins deficiency
DNA-Binding Proteins genetics
Female
Humans
In Vitro Techniques
Keratinocytes metabolism
Keratinocytes pathology
Keratinocytes radiation effects
Ligands
Lipid Metabolism genetics
Liver X Receptors
Mice
Mice, Hairless
Mice, Knockout
Models, Biological
Orphan Nuclear Receptors
Receptors, Cytoplasmic and Nuclear deficiency
Receptors, Cytoplasmic and Nuclear genetics
Skin Aging pathology
DNA-Binding Proteins metabolism
Receptors, Cytoplasmic and Nuclear metabolism
Skin Aging physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0888-8809
- Volume :
- 22
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecular endocrinology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 18787039
- Full Text :
- https://doi.org/10.1210/me.2008-0232