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

• Published in: British journal of dermatology (1951) Vol. 165; no. 2; pp. 285 - 291
• Main Authors: Kumar, R., Parsad, D., Kanwar, A.J., Kaul, D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2011; Wiley-Blackwell
• Subjects: Adult; Biological and medical sciences; Biopsy; Biopsy, Needle; Case-Control Studies; Cell culture; Cell migration; Cells, Cultured; Dermatology; Epidermis; Follicles; Gelatin; Gelatinase A; Gelatinase B; Hair; Humans; Interstitial collagenase; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Melanocytes; Melanocytes - enzymology; Melanocytes - metabolism; Pigmentary diseases of the skin; Polymerase chain reaction; Proto-Oncogene Protein c-ets-1 - metabolism; RNA, Messenger - metabolism; Roots; Sheaths; Skin; Skin - enzymology; Skin - pathology; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transcription factors; Translation; Vitiligo; Vitiligo - metabolism; Vitiligo - pathology; Western blotting; Young Adult; Human; Peptidases; Skin disease; Vitiligo; Pigmentation disorder; Enzyme; Dermatology; Hydrolases; Metalloendopeptidases; Transcription factor; Interstitial collagenase
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2011.10324.x

Summary
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.