title: In vitro investigations on the effect of dermal fibroblasts on keratinocyte responses to ultraviolet B radiation.
abstract: Exposure to ultraviolet radiation is closely linked to the development of skin cancers in humans. The ultraviolet B (UVB) radiation wavelength (280-320 nm), in particular, causes DNA damage in epidermal keratinocytes, which are linked to the generation of signature premalignant mutations. Interactions between dermal fibroblasts and keratinocytes play a role in epidermal repair and regeneration after UVB-induced damage. To investigate these processes, established two and three-dimensional culture models were utilized to study the impact of fibroblast-keratinocyte crosstalk during the acute UVB response. Using a coculture system it was observed that fibroblasts enhanced keratinocyte survival and the repair of cyclobutane pyrimidine dimers (CPDs) after UVB radiation exposure. These findings were also mirrored in irradiated human skin coculture models employed in this study. Fibroblast coculture was shown to play a role in the expression and activation of members of the apoptotic cascade, including caspase-3 and Bad. Interestingly, the expression and phosphorylation of p53, a key player in the regulation of keratinocyte cell fate postirradiation, was also shown to be influenced by fibroblast-produced factors. This study highlights the importance of synergistic interactions between fibroblasts and keratinocytes in maintaining a functional epidermis while promoting repair and regeneration following UVB radiation-induced damage.
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Qld, Australia.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Fernandez
authors.forename: Derek R
authors.initials: DR
authors.lastname: Van Lonkhuyzen
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Dawson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kimlin
authors.forename: Zee
authors.initials: Z
authors.lastname: Upton
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D002478:Cells, Cultured; D018920:Coculture Techniques; D017931:DNA Primers; D004260:DNA Repair; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000528:radiation effects*; D012867:Skin / Q000166:cytology / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers