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.

Evaluation of the Secretome Profile and Functional Characteristics of Human Bone Marrow Mesenchymal Stromal Cells-Derived Conditioned Medium Suggest Potential for Skin Rejuvenation

“…This cross talk between the fibroblasts and keratinocytes involves proliferation and DNA repair of the latter cell type [28] [29]. In this study, we have demonstrated anti-aging and anti-wrinkling potential of BMMSC derived CM using a comprehensive multiparametric analysis by inducing oxidative stress and UV-B damage in dermal fibroblast system in vitro.…”

Attenuated kallikrein‐related peptidase activity disrupts desquamation and leads to stratum corneum thickening in human skin equivalent models

“…Human skin equivalents are commonly employed as preclinical models to study, for example, the mechanistic and biological aspects of wound healing, skin sensitizers and the role of ultraviolet (UV) light in DNA damage. [35][36][37] However, it has previously been reported that HSE models develop an overly thick stratum corneum, 15,16 which has important implications for skin research. For example, increased thickness of the stratum corneum can affect the penetration of UV light and, consequently, its biological effects.…”

Insulin‐like growth factor‐I and UVB photoprotection in human keratinocytes

“…Recently, we describe fibroblast-keratinocyte crosstalk as a modulator of UVB-induced effects in the epidermis (4). Herein, we analysed the effect of IGF-I (as a major pathway in this crosstalk) in (i) the survival, (ii) cell cycle progression, (iii) repair of CPDs and (iv) expression of DNA damage response proteins in irradiated human keratinocytes in vitro.…”

“…According to Yoshimura's 'three zones theory' of cell survival, only adipocytes in the most superficial layer (about 300 lm from the graft surface) are in the 'surviving zone', while the rest almost all die within 24 h after transplantation (4). Although the Coleman technique is designed to protect the activity and integrity of the adipocytes, the majority do not survive.…”