P-cadherin regulates human hair growth and cycling via canonical wnt signaling and transforming growth factor-β2

Liat Samuelov, Eli Sprecher, Daisuke Tsuruta, Tamás Bíró, Jennifer E. Kloepper, Ralf Paus

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

P-cadherin is a key component of epithelial adherens junctions, and it is prominently expressed in the hair follicle (HF) matrix. Loss-of-function mutations in CDH3, which encodes P-cadherin, result in hypotrichosis with juvenile macular dystrophy (HJMD), an autosomal recessive disorder featuring sparse and short hair. Here, we attempted to recapitulate some aspects of HJMD in vitro by transfecting normal, organ-cultured human scalp HFs with lipofectamine and CDH3-specific or scrambled control siRNAs. As in HJMD patients, P-cadherin silencing inhibited hair shaft growth, prematurely induced HF regression (catagen), and inhibited hair matrix keratinocyte proliferation. In situ, membrane Β-catenin expression and transcription of the Β-catenin target gene, axin2, were significantly reduced, whereas glycogen synthase kinase 3 Β (GSK3Β) and phospho-Β-catenin immunoreactivity were increased. These effects were partially reversed by inhibiting GSK3Β. P-cadherin silencing reduced the expression of the anagen-promoting growth factor, IGF-1, whereas that of transforming growth factor Β 2 (TGFΒ2; catagen promoter) was enhanced. Neutralizing TGFΒ antagonized the catagen-promoting effects of P-cadherin silencing. In summary, we introduce human HFs as an attractive preclinical model for studying the functions of P-cadherin in human epithelial biology and pathology. This model demonstrates that cadherins can be successfully knocked down in an intact human organ in vitro, and shows that P-cadherin is needed for anagen maintenance by regulating canonical Wnt signaling and suppressing TGFΒ2.

Original languageEnglish
Pages (from-to)2332-2341
Number of pages10
JournalJournal of Investigative Dermatology
Volume132
Issue number10
DOIs
Publication statusPublished - Oct 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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