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Topobiology of Human Pigmentation: P-Cadherin Selectively Stimulates Hair Follicle Melanogenesis.
MedLine Citation:
PMID:  23334344     Owner:  NLM     Status:  Publisher    
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. Since 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, while 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 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.Journal of Investigative Dermatology accepted article preview online, 18 January 2013; doi:10.1038/jid.2013.18.
Liat Samuelov; Eli Sprecher; Koji Sugawara; Suman K Singh; Desmond J Tobin; Daisuke Tsuruta; Tamás Bíró; Jennifer E Kloepper; Ralf Paus
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-18
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  -     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1] Department of Dermatology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel [2] Department of Dermatology, University of Luebeck, Luebeck, Germany.
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