Immunohistochemical Analysis of GDNF and Its Cognate Receptor GFRα-1 Protein Expression in Vitiliginous Skin Lesions.
BACKGROUND
Vitiligo is an idiopathic skin disease, characterized by circumscribed white macules or patches on the skin due to loss of the functional melanocytes. Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are distal members of the transforming growth factor-β superfamily. GDNF, produced by the basal cell keratinocytes, is involved in the migration and differentiation of the melanocytes from the neural crest to the epidermis. This study examines the hypothesis that expression of GDNF protein and its cognate receptor GFRα-1 protein is altered in vitiliginous skin.


METHODS
To test our hypothesis, we examined the expression patterns of these proteins in vitiliginous and corresponding healthy (control) skin biopsies (20 specimens each) using immunoperoxidase staining techniques.


RESULTS
We found variations between the vitiliginous skin and healthy skin. In healthy skin, the expression of GDNF and GFRα-1 proteins was strong (basal cell keratinocytes and melanocytes), moderate (spinous layer), and weak (granular cell layer). In contrast, weak expression of GDNF protein was observed in all epidermal layers of vitiliginous skin. GFRα-1 protein expression was strong (basal cell keratinocytes and melanocytes), moderate (spinous layer), and weak (granular cell layer). In both healthy skin and vitiliginous skin, the expression of GDNF and GFRα-1 proteins was strong in the adnexal structures.


CONCLUSIONS
We report, for the first time, decreased expression of GDNF proteins in the epidermal keratinocytes of vitiliginous skin. Our findings suggest possible pathogenetic roles for these proteins in the development of vitiligo. The clinical ramifications of these observations mandate further investigations.
Department of Zoology, Faculty of Science, Sohag University, Sohag, Egypt m.adly@yahoo.com.
Mohamed A
MA
Adly
Department of Dermatology and Venereology, Faculty of Medicine, Sohag University, Sohag, Egypt.
Hanan A
HA
Assaf
Department of Dermatology and Venereology, Faculty of Medicine, Aswan University, Aswan, Egypt.
Shaima'a F
SF
Abdel-Rady
Department of Biochemistry, Faculty of Medicine, Sohag University, Egypt.
Nagwa Sayed
NS
Ahmed
Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Mahmoud Rezk Abdelwahed
MR
Hussein
D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D014820:Vitiligo / Q000378:metabolism* / Q000473:pathology
C495039:GDNF protein, human; C494987:GFRA1 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors
GDNF; GFRα-1; healthy skin; vitiligo