title: Altered levels of LXR-α: crucial implications in the pathogenesis of vitiligo.
abstract: In recent times, the role of LXRs in skin physiology and pathology has evolved rapidly because of their role in proliferation, carcinogenesis, differentiation and permeability barrier function. LXRs were identified as promising drug targets for the treatment of many skin diseases. For this study, skin biopsies were taken from 15 patients with vitiligo and six controls to culture melanocytes from clinically active perilesional and normal skin. Gene expression was examined by reverse transcriptase-polymerase chain reaction analysis. Role of LXR-α in regulating the expression of MMPs was checked by gene knock-down, and its role in vitiligo pathogenesis was checked by treatment with LXR-α agonist 22(R)-hydroxycholesterol. After treatment adhesion assay, annexin V staining and proliferation assay were performed. The expression of LXR-α was relatively more in perilesional skin melanocytes as compared to uninvolved skin melanocytes of non-segmental vitiligo patient, and controls on the other hand, perilesional melanocytes were more prone to apoptosis. LXR-α gene knock-down significantly increases the expression of MMPs. LXR-α agonist 22(R)-hydroxycholesterol treatment significantly decreases melanocyte adhesion, apoptosis and proliferation. Higher expression of LXR-α in perilesional skin melanocytes significantly decreases the adhesion, proliferation and matrix metalloproteinases and increases apoptosis.
authors.affiliation: Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Kumar
authors.forename: Davinder
authors.initials: D
authors.lastname: Parsad
authors.forename: Amrinderjit J
authors.initials: AJ
authors.lastname: Kanwar
authors.forename: Amrinderjit
authors.initials: A
authors.lastname: Kanwar
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaul
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D000071518:Liver X Receptors; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014820:Vitiligo / Q000209:etiology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D006888:Hydroxycholesterols; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; C003585:22-hydroxycholesterol; D020782:Matrix Metalloproteinases