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The expression of the c-kit receptor by epidermal melanocytes may be reduced in vitiligo
Abstract:
The proto-oncogene c-kit encodes the transmembrane tyrosine kinase receptor that has a role in the growth regulation of various cell types including melanocytes. In the present study we have examined the expression of the c-kit protein in the skin of seven patients with vitiligo. Melanocytes positive for c-kit protein were observed in the basal layer in non-lesional skin and the mean number of 25.8 +/- 5.2 (per 200 basal cells) compared with that of 21.8 +/- 3.5 from six control subjects. In perilesional skin there was a reduction in the numbers of c-kit positive melanocytes (6.7 +/- 2.6) and this was especially noticeable in six of the seven patients. Such a reduction was less obvious following staining with MEL-5 and in only two subjects were the numbers of melanocytes below the normal range. This suggests that the reduction in c-kit staining was the result of decreased expression of the protein rather than a loss of melanocytes. No melanocytes, positive for c-kit protein, or after staining with MEL-5, were identified in lesional skin although isolated tyrosinase-positive melanocytes were seen in one subject. There was no apparent change in the numbers of mast cells expressing c-kit protein and the intensity of staining in the dermis even in lesional skin was similar to that in the controls. These results demonstrate that c-kit protein is present on melanocytes in adult human skin and that in perilesional skin of some vitiligo patients there is a reduction in the numbers of melanocytes expressing this receptor. Whether this may contribute to the defective melanocyte growth and/or survival that occurs in vitiligo or whether it is a consequence of melanocyte damage remains to be seen.
Insights
Vitiligo patients show reduced c-kit protein expression on melanocytes in skin surrounding lesions. This suggests altered c-kit signaling may impact melanocyte function in vitiligo.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- The proto-oncogene c-kit encodes a receptor tyrosine kinase crucial for melanocyte growth.
- Vitiligo is a condition characterized by the loss of melanocytes, leading to skin depigmentation.
Purpose of the Study:
- To investigate the expression of c-kit protein in the skin of vitiligo patients.
- To determine if c-kit expression is altered in lesional and perilesional skin compared to controls.
Main Methods:
- Immunohistochemical analysis of c-kit protein expression in skin biopsies from vitiligo patients and healthy controls.
- Quantification of c-kit positive melanocytes in the basal layer of non-lesional, perilesional, and lesional skin.
- Comparison of c-kit expression with MEL-5 staining to differentiate between protein reduction and melanocyte loss.
Main Results:
- Non-lesional skin showed similar numbers of c-kit positive melanocytes in vitiligo patients and controls.
- Perilesional skin exhibited a significant reduction in c-kit positive melanocytes in most vitiligo patients.
- Lesional skin lacked detectable c-kit positive melanocytes, with reduced c-kit staining suggesting decreased protein expression rather than melanocyte absence.
Conclusions:
- c-kit protein is expressed on melanocytes in adult human skin.
- Vitiligo is associated with reduced c-kit expression on melanocytes in perilesional skin.
- The functional significance of diminished c-kit expression in vitiligo pathogenesis requires further investigation.