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dc.contributor.authorSamuelov, L.*
dc.contributor.authorSprecher, E.*
dc.contributor.authorSugawara, K.*
dc.contributor.authorSingh, Suman K.*
dc.contributor.authorTobin, Desmond J.*
dc.contributor.authorTsuruta, D.*
dc.contributor.authorBíró, T.*
dc.contributor.authorKloepper, J.E.*
dc.contributor.authorPaus, R.*
dc.date.accessioned2015-03-13T16:11:57Z
dc.date.available2015-03-13T16:11:57Z
dc.date.issued2013
dc.identifier.citationSamuelov 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.en_US
dc.identifier.urihttp://hdl.handle.net/10454/7143
dc.descriptionnoen_US
dc.description.abstractP-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.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://www.nature.com/jid/journal/v133/n6/abs/jid201318a.htmlen_US
dc.subjectTopobiology; Human Pigmentation; P-Cadherin; Hair Follicles; Hair Follicle Melanogenesis; Mammalian epitheliumen_US
dc.titleTopobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesisen_US
dc.status.refereedYesen_US
dc.typeArticleen_US
dc.type.versionNo full-text available in the repositoryen_US


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