title: Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial-mesenchymal interaction.
abstract: BACKGROUND
  Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood.
  
  
  OBJECTIVE
  This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging.
  
  
  METHODS
  Dermal papilla cells were challenged with H2O2to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo.
  
  
  RESULTS
  Dermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo.
  
  
  CONCLUSIONS
  Stress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Yen
authors.initials: WY
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Kai-Shin
authors.initials: KS
authors.lastname: Huang
authors.affiliation: Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chan
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan.
authors.forename: Hsien-Yi
authors.initials: HY
authors.lastname: Chiu
authors.affiliation: Department of Dermatology and Skin Laser Center, Taipei Municipal Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ren-Yeu
authors.initials: RY
authors.lastname: Tsai
authors.affiliation: Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Department of Dermatology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Jung-Yi
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan; Center for Molecular Imaging, National Taiwan University, Taipei, Taiwan. Electronic address: drsjlin@ntu.edu.tw.
authors.forename: Sung-Jan
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006197:Hair / Q000254:growth & development; D018859:Hair Follicle / Q000166:cytology* / Q000473:pathology*; D006861:Hydrogen Peroxide / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012867:Skin / Q000254:growth & development / Q000473:pathology*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D006861:Hydrogen Peroxide
keywords: Aging; Alopecia; Epithelial-mesenchymal interaction; Premature senescence; Stem cell