Transcriptomic analysis and identification of paracrine factors responsible for protective effects of keratinocytes on UVB-mediated melanocyte responses

Ultraviolet radiation (UVR) is detrimental to human skin through triggering various types of cellular damage accountable for photodamage and increased risk of developing skin cancers including cutaneous non-melanoma and melanoma. UVB irradiation can cause the loss of cellular integrity, direct damage to DNA and mediate cellular responses including apoptosis and oxidative stress in skin cells including melanocytes (MC). We previously reported that nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant defenses, in keratinocytes (KC) played a protective role in UVB-induced DNA damage and apoptosis in MC. In this study, we will employ transcriptomic approaches to determine the candidate paracrine factors secreted by KC responsible for their protective effects on UVB-mediated MC responses including oxidative stress, apoptosis and melanogenesis. Then, the protective effects of the candidate paracrine factors on UVB-induced MC responses will be determined using small-interfering RNA-mediated silencing of the candidate paracrine factor (siPF) in MC-KC co-culture system and mouse model of photoaging.