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Liver X receptor is a therapeutic target for photoaging and chronological skin aging

Cited 36 time in Web of Science Cited 35 time in Scopus
Authors
Chang, Ken C N; Shen, Qi; Oh, Inn Gyung; Jelinsky, Scott A; Jenkins, Susan F; Wang, Wei; Wang, Yihe; LaCava, Margaret; Yudt, Matthew R; Thompson, Catherine C; Freedman, Leonard P; Chung, Jin Ho; Nagpal, Sunil
Issue Date
2008-09-13
Publisher
Endocrine Society
Citation
Mol Endocrinol. 22(11):2407-2419
Keywords
AnimalsCell DifferentiationCells, CulturedDNA-Binding Proteins/deficiency/genetics/*metabolismFemaleHumansKeratinocytes/metabolism/pathology/radiation effectsLigandsLipid Metabolism/geneticsMiceMice, HairlessMice, KnockoutModels, BiologicalReceptors, Cytoplasmic and Nuclear/deficiency/genetics/*metabolismSkin Aging/pathology/*physiology
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.
ISSN
0888-8809 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18787039

http://mend.endojournals.org/cgi/reprint/22/11/2407.pdf

http://hdl.handle.net/10371/67525
DOI
https://doi.org/10.1210/me.2008-0232
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College of Medicine/School of Medicine (의과대학/대학원)Dermatology (피부과학전공)Journal Papers (저널논문_피부과학전공)
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