Altered levels of LXR-alpha: crucial implications in the pathogenesis of vitiligo

作者:Kumar Ravinder; Parsad Davinder*; Kanwar Amrinderjit; Kaul Deepak
来源:Experimental Dermatology, 2012, 21(11): 853-858.
DOI:10.1111/exd.12017

摘要

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-alpha in regulating the expression of MMPs was checked by gene knockdown, and its role in vitiligo pathogenesis was checked by treatment with LXR-alpha agonist 22(R)-hydroxycholesterol. After treatment adhesion assay, annexin V staining and proliferation assay were performed. The expression of LXR-alpha 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-alpha gene knock-down significantly increases the expression of MMPs. LXR-alpha agonist 22(R)-hydroxycholesterol treatment significantly decreases melanocyte adhesion, apoptosis and proliferation. Higher expression of LXR-alpha in perilesional skin melanocytes significantly decreases the adhesion, proliferation and matrix metalloproteinases and increases apoptosis.