Related resources
Full-text held externally
- PMID: 23334344
- UKPMCID: 23334344
- DOI: 10.1038/jid.2013.18
Search for item elsewhere
University researcher(s)
Academic department(s)
Topobiology of Human Pigmentation: P-Cadherin Selectively Stimulates Hair Follicle Melanogenesis.
Samuelov, Liat; Sprecher, Eli; Sugawara, Koji; Singh, Suman K; Tobin, Desmond J; Tsuruta, Daisuke; BĂrĂł, Tamás; Kloepper, Jennifer E; Paus, Ralf
The Journal of investigative dermatology. 2013;.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- PMID: 23334344
- UKPMCID: 23334344
- DOI: 10.1038/jid.2013.18
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.Journal of Investigative Dermatology advance online publication, 28 February 2013; doi:10.1038/jid.2013.18.