Altered levels of Ets-1 transcription factor and matrix metalloproteinases in melanocytes from patients with vitiligo.

摘要

BACKGROUND: Vitiligo is characterized by the loss of functional melanocytes from the epidermis. Repigmentation in vitiligo is initiated by activation, proliferation and migration of melanoblasts from the outer root sheath of hair follicles, or melanocytes from the border area of vitiligo lesions, into the depigmented epidermis. Cell migration plays a crucial role during repigmentation in vitiligo. OBJECTIVES: To investigate the role of matrix metalloproteinases (MMPs) and their transcription factor Ets-1 in vitiligo. METHODS: Skin biopsies were taken from 15 patients with vitiligo and six controls to culture melanocytes from clinically active perilesional and normal skin. Expression of MMP-1, MMP-2, MMP-9 and Ets-1 was examined by reverse transcriptase-polymerase chain reaction analysis. Expression of Ets-1 was also confirmed with Western blot analysis. Activity of MMP-2 and MMP-9 was assessed using gelatin zymography. RESULTS: The activity of MMP-2 and MMP-9 was significantly lower in patients with vitiligo compared with the controls. The expression of MMP-2 and MMP-9 was also significantly lower in patients with vitiligo. There was no expression of Ets-1 transcription factor at either the transcriptional or translational level in melanocytes cultured from patients with vitiligo. CONCLUSION: The absence of a basal level of expression of Ets-1 significantly decreases the expression and activity of MMP-2 and MMP-9. Significant decreases in MMP-2 and MMP-9 activity could possibly reduce the migration of melanocyte precursors (melanoblasts) from the outer root sheath of hair follicles or migration of melanocytes from the border of vitiligo lesions into clinically depigmented epidermis which is crucial to the repigmentation of vitiliginous skin.