Poster Presentation 6th Australian Health and Medical Research Congress 2012

Dermal fibroblasts promote epidermal repair and regeneration in a 3D skin equivalent model. (#334)

Tara L Fernandez 1 , Van Lonkhuyzen Derek 1 , Leavesley David 1 , Dawson Rebecca 1 , Kimlin G Michael 2 , Upton Zee 1
  1. Institute of Health & Biomedical Innovation, Kelvin Grove, QLD, Australia
  2. AusSun Research Laboratory, Queensland University of Technology, Brisbane, QLD, Australia

The extreme level of ultraviolet radiation (UVR) experienced in Australia is associated with rapidly-increasing incidences of UVR-induced melanomas and non-melanoma skin cancers. The UVB wavelength penetrates the skin’s epidermis generating photolesions and cell damage. Intrinsic protective mechanisms in keratinocytes safeguard against photocarcinogenesis by activating repair or pro-apoptotic mechanisms. Dermal fibroblasts are known to stimulate and regulate developmental, homeostatic and regenerative processes in the epidermis via the action of various secreted factors. How fibroblast-keratinocyte interactions influence epidermal responses to UVB, however, has yet to be fully defined, in part due to the limited availability of physiologically-relevant in vitro models. A 3-dimensional human skin equivalent (HSE) model consisting of primary human keratinocytes and fibroblasts seeded on an ex vivo dermal scaffold was adopted to investigate the role of epidermal-dermal interactions in the UVB radiation response. Keratinocytes in irradiated HSE composites mirrored responses to those observed in vivo, such as the formation of DNA dimers and sunburn cells. Following UVB treatment, keratinocytes initiated a DNA repair response and showed altered proliferation and differentiation patterns. These UVB-induced epidermal changes were modulated as a result of fibroblast-secreted factors, by increasing the rate of DNA damage repair, inhibiting apoptosis and promoting regeneration. These pro-survival and repair effects induced by fibroblasts were shown to be dependent on the action of p53 and the direct inhibition of apoptotic pathways. The insulin-like growth factor system was also found to be a key player in mediating fibroblast-induced epidermal regeneration following UVB-exposure.