title: Decreased expression of keratinocyte beta1 integrins in chronically sun-exposed skin in vivo.
abstract: BACKGROUND
  Chronic exposure to ultraviolet (UV) radiation induces changes in the skin structure which are mostly found in the superficial dermis and at the dermal-epidermal junction. Keratinocytes and fibroblasts contribute both to the synthesis and to the degradation of the molecules important for the integrity of this skin site. While several studies have reported on alterations of dermal components and of the functions of fibroblasts in vivo and in vitro after UV exposure, recent data suggested that keratinocytes could be the main skin cell type involved in the photoageing process.
  
  
  OBJECTIVE
  In this study, we analysed the expression of two keratinocyte molecules namely, beta1 integrin (a proliferation marker) and involucrin (a differentiation marker) in sun-exposed and sun-protected facial skin of 16 healthy patients undergoing facial lifting.
  
  
  METHODS
  Methods included histology, immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis.
  
  
  RESULTS
  Sun-exposed skin displayed the characteristic morphological and molecular features of dermal photoageing, compared with sun-protected skin, including dermal elastosis, diminished fibrillin and type VII collagen expression. Analysis of the epidermis in sun-exposed vs. sun-protected skin showed no histological differences, but dramatic changes in the expression of beta1 integrin and involucrin. In sun-exposed skin, expression of beta1 integrin protein by epidermal basal cells was reduced, paralleling a downregulation of beta1 integrin mRNA, whereas involucrin protein expression was greatly enhanced in the superficial epidermal cell layers. Interestingly, the ratio between involucrin and beta1 integrin protein expression was consistently increased in sun-exposed skin sites.
  
  
  CONCLUSIONS
  Collectively these results demonstrate that epidermal homeostasis is impaired by chronic UV exposure, and define beta1 integrin expression as a molecular marker of the epidermal photoageing process.
authors.affiliation: INSERM U503, Université Claude Bernard et Hospices Civils de Lyon, 21 Av. Tony Garnier, 69007 Lyon, France. bosset@cervi-lyon.inserm.fr
authors.forename: S
authors.initials: S
authors.lastname: Bosset
authors.forename: M
authors.initials: M
authors.lastname: Bonnet-Duquennoy
authors.forename: P
authors.initials: P
authors.lastname: Barré
authors.forename: A
authors.initials: A
authors.lastname: Chalon
authors.forename: K
authors.initials: K
authors.lastname: Lazou
authors.forename: R
authors.initials: R
authors.lastname: Kurfurst
authors.forename: F
authors.initials: F
authors.lastname: Bonté
authors.forename: S
authors.initials: S
authors.lastname: Schnébert
authors.forename: F
authors.initials: F
authors.lastname: Disant
authors.forename: B
authors.initials: B
authors.lastname: Le Varlet
authors.forename: J F
authors.initials: JF
authors.lastname: Nicolas
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D024043:Collagen Type II / Q000378:metabolism; D015536:Down-Regulation / Q000528:radiation effects; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D005145:Face / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D018613:Microscopy, Confocal; D008875:Middle Aged; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015595:Skin Aging / Q000473:pathology / Q000528:radiation effects*; D013472:Sunlight; D014466:Ultraviolet Rays
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D019012:Integrin beta1; D011498:Protein Precursors; D012333:RNA, Messenger; C032253:involucrin