RESUMO
The activation status of the insulin-like growth factor-1 receptor (IGF-1R) regulates the cellular response of keratinocytes to ultraviolet B (UVB) exposure, both in vitro and in vivo. Geriatric skin is deficient in IGF-1 expression resulting in an aberrant IGF-1R-dependent UVB response which contributes to the development of aging-associated squamous cell carcinoma. Furthermore, our lab and others have reported that geriatric keratinocytes repair UVB-induced DNA damage less efficiently than young adult keratinocytes. Here, we show that IGF-1R activation influences DNA damage repair in UVB-irradiated keratinocytes. Specifically, in the absence of IGF-1R activation, the rate of DNA damage repair following UVB-irradiation was significantly slowed (using immortalized human keratinocytes) or inhibited (using primary human keratinocytes). Furthermore, inhibition of IGF-1R activity in human skin, using either ex vivo explant cultures or in vivo xenograft models, suppressed DNA damage repair. Primary keratinocytes with an inactivated IGF-1R also exhibited lower steady-state levels of nucleotide excision repair mRNAs. These results suggest that deficient UVB-induced DNA repair in geriatric keratinocytes is due in part to silenced IGF-1R activation in geriatric skin and provide a mechanism for how the IGF-1 pathway plays a role in the initiation of squamous cell carcinoma in geriatric patients.
Assuntos
Dano ao DNA , Reparo do DNA/efeitos da radiação , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Receptor IGF Tipo 1/metabolismo , Raios Ultravioleta , Animais , Células Cultivadas , Reparo do DNA/genética , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Cinética , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Telomerase/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The demand for skin resurfacing and rejuvenating procedures has progressively increased in the last decade and has sparked several advances within the skin resurfacing field that promote faster healing while minimizing downtime and side effects for patients. Several technological and procedural skin resurfacing developments are being integrated into clinical practices today allowing clinicians to treat a broader range of patients' skin types and pathologies than in years past, with noteworthy outcomes. This article will discuss some emerging and developing resurfacing therapies and treatments that are present today and soon to be available.
