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Topobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesis

Samuelov, L.
; 
Sprecher, E.
; 
Sugawara, K.
; 
Singh, Suman K.
; 
Tobin, Desmond J.
; 
Tsuruta, D.
; 
Bíró, T.
; 
Kloepper, J.E.
; 
Paus, R.
Publication Date
2013
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Keywords
Topobiology, Human Pigmentation, P-Cadherin, Hair Follicles, Hair Follicle Melanogenesis, Mammalian epithelium
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Abstract
P-cadherin serves as a major topobiological cue in mammalian epithelium. In human hair follicles (HFs), it is prominently expressed in the inner hair matrix that harbors the HF pigmentary unit. However, the role of P-cadherin in normal human pigmentation remains unknown. As patients with mutations in the gene that encodes P-cadherin show hypotrichosis and fair hair, we explored the hypothesis that P-cadherin may control HF pigmentation. When P-cadherin was silenced in melanogenically active organ-cultured human scalp HFs, this significantly reduced HF melanogenesis and tyrosinase activity as well as gene and/or protein expression of gp100, stem cell factor, c-Kit, and microphthalmia-associated transcription factor (MITF), both in situ and in isolated human HF melanocytes. Instead, epidermal pigmentation was unaffected by P-cadherin knockdown in organ-cultured human skin. In hair matrix keratinocytes, P-cadherin silencing reduced plasma membrane β-catenin, whereas glycogen synthase kinase 3 beta (GSK3β) and phospho-β-catenin expression were significantly upregulated. This suggests that P-cadherin-GSK3β/Wnt signaling is required for maintaining the expression of MITF to sustain intrafollicular melanogenesis. Thus, P-cadherin-mediated signaling is a melanocyte subtype-specific topobiological regulator of normal human pigmentation, possibly via GSK3β-mediated canonical Wnt signaling.
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http://hdl.handle.net/10454/7143
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Citation
Samuelov L, Sprecher E, Sugawara K et al (2013) Topobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesis. Journal of Investigative Dermatology. 133(6): 1591-600.
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https://doi.org/10.1038/jid.2013.18
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