| Topobiology of Human Pigmentation: P-Cadherin Selectively Stimulates Hair Follicle Melanogenesis. | |
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MedLine Citation:
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PMID: 23334344 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-18 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: - ISSN: 1523-1747 ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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