S-Space College of Medicine/School of Medicine (의과대학/대학원) Dermatology (피부과학전공) Journal Papers (저널논문_피부과학전공)
Estrogen Receptor β Is a Novel Therapeutic Target for Photoaging
Cited 23 time in Web of Science Cited 29 time in Scopus
- Issue Date
- MOLECULAR PHARMACOLOGY; Vol.77, no.5; 744-750
- One of the many harmful factors faced by the skin is solar UV radiation, which damages skin by inducing chronic low-grade inflammation through increased expression of proinflammatory cytokines, metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). Estrogen receptors (ERs) alpha and beta are ligand-dependent transcription factors that are expressed in skin, and an ER beta agonist has previously shown efficacy in vivo in models of pain and inflammation. Because ER beta does not carry the breast and uterine proliferation liabilities of ER alpha, we decided to explore the possibility of using ER beta as a target for photoaging. We show that ER beta-selective compounds suppressed the expression of cytokines and MMPs in activated keratinocytes and fibroblast-based in vitro models of photoaging. Furthermore, in activated dermal fibroblasts, ER beta-selective compounds also inhibited COX-2. These activities of ER beta ligands in skin cells correlated with the expression levels of ER beta and showed reversal by treatment with a potent synthetic ER antagonist. Furthermore, the pharmacology of ER beta-selective compound was observed in wild-type but not in skin cells obtained from ER beta knockout mice. Finally, we demonstrate that a synthetic ER beta agonist inhibited UV-induced photo-damage and skin wrinkle formation in a murine model of photoaging. Therefore, the potential of an ER beta ligand to regulate multiple pathways underlying the cause of photoaging suggests ER beta to be a novel therapeutic target for the prevention and treatment of photoaging.
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