title: Premature senescence of balding dermal papilla cells in vitro is associated with p16(INK4a) expression.
abstract: Androgenetic alopecia (AGA), a hereditary disorder that involves the progressive thinning of hair in a defined pattern, is driven by androgens. The hair follicle dermal papilla (DP) expresses androgen receptors (AR) and plays an important role in the control of normal hair growth. In AGA, it has been proposed that the inhibitory actions of androgens are mediated via the DP although the molecular nature of these interactions is poorly understood. To investigate mechanisms of AGA, we cultured DP cells (DPC) from balding and non-balding scalp and confirmed previous reports that balding DPC grow slower in vitro than non-balding DPC. Loss of proliferative capacity of balding DPC was associated with changes in cell morphology, expression of senescence-associated beta-galactosidase, as well as decreased expression of proliferating cell nuclear antigen and Bmi-1; upregulation of p16(INK4a)/pRb and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase catalase, ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. Premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPC are sensitive to environmental stress and identifies alternative pathways that could lead to novel therapeutic strategies for treatment of AGA.
authors.affiliation: Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, Queen Mary College, London, UK.
authors.forename: Adiam W
authors.initials: AW
authors.lastname: Bahta
authors.forename: Nilofer
authors.initials: N
authors.lastname: Farjo
authors.forename: Bessam
authors.initials: B
authors.lastname: Farjo
authors.forename: Mike P
authors.initials: MP
authors.lastname: Philpott
mesh_terms: D000505:Alopecia / Q000378:metabolism* / Q000473:pathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D002374:Catalase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D020405:Dermis / Q000378:metabolism / Q000473:pathology*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D063150:Polycomb Repressive Complex 1; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C000606290:SOD1 protein, human; D025521:Tumor Suppressor Proteins; D002374:Catalase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D063150:Polycomb Repressive Complex 1; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases