UVA exposure of human skin reconstructed in vitro induces apoptosis of dermal fibroblasts: subsequent connective tissue repair and implications in photoaging

Abstract

The skin reconstructed in vitro has been previously shown to be a useful model to investigate the effects of UVB exposure (Bernerd and Asselineau, 1997). The present study describes the response to UVA irradiation. Major alterations were observed within the dermal compartment. Apoptosis of fibroblasts located in the superficial area of the dermal equivalent was observed as soon as 6 h after irradiation, leading to their disappearance after 48 h. This effect was obtained without major alterations of epidermal keratinocytes suggesting a differential cell type sensitivity to UVA radiations. In addition, collagenase I was secreted by dermal fibroblasts. The UVA dermal effects could be observed even after removal of the epidermis during the post irradiation period, demonstrating that they were independent of the keratinocyte response. The analysis of the tissue regeneration during the following 2 weeks revealed a connective tissue repair via fibroblasts proliferation, migration and active synthesis of extracellular matrix proteins such as fibronectin and procollagen I. This cellular recolonization of the superficial part of the dermal equivalent was due to activation of surviving fibroblasts located deeply in the dermal equivalent. The direct damage in the dermis and the subsequent connective tissue repair may contribute to the formation of UVA-induced dermal alterations.

Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes

“…Very importantly, overexpression of galectin-7 in sunburn keratinocytes also was observed in human skin ex vivo after UVB irradiation. The present findings put forward the role of galectin-7 in UVBinduced apoptosis of epidermal keratinocytes and further support previous studies (20,47,48) regarding the usefulness of skin reconstructed in vitro in evaluating effectors of cell fate and differentiation in epidermis.…”

Ultraviolet A-induced Modulation of Bcl-XL by p38 MAPK in Human Keratinocytes

“…Pourzand et al (51) reported UVAinduced apoptosis through antioxidant properties of Bcl-2 in Rat 6 fibroblasts. Studies by Bernerd et al (52) demonstrate that UVA induces apoptosis of fibroblasts in the dermis without significant effects on kertinocytes residing in the epidermis by using an in vitro reconstructed skin model. These data suggest a differential effect of UVA on sensitivity to apoptosis depending upon cell type.…”

Fibroblast heterogeneity: more than skin deep

“…These situations were repaired in skin equivalents that were maintained in culture for extended periods of time. In another study, they found that UVA exposure induces responses specific to the dermal compartment of skin equivalents (Bernerd and Asselineau, 1998). Fibroblasts in the upper regions of the 'dermal' component of the skin equivalents underwent apoptosis and disappeared from the constructs.…”