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Altered levels of LXR ‐α: crucial implications in the pathogenesis of vitiligo
Author(s) -
Kumar Ravinder,
Parsad Davinder,
Kanwar Amrinderjit,
Kaul Deepak
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12017
Subject(s) - vitiligo , liver x receptor , melanocyte , pathogenesis , matrix metalloproteinase , apoptosis , cancer research , biology , gene expression , medicine , melanoma , immunology , transcription factor , gene , biochemistry , nuclear receptor
In recent times, the role of LXR s in skin physiology and pathology has evolved rapidly because of their role in proliferation, carcinogenesis, differentiation and permeability barrier function. LXR s 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 MMP s 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 MMP s. 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.