CELL SIGNALING LEADING TO UV-INDUCED CELL INJURY

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Long-term exposure to UV radiation causes wrinkles. The water content and water-holding capacity of the skin often decrease after exposure to UV, leading to deleterious effects such as wrinkles and delayed wound healing. While cosmetic facial masks remains one of the most popular approaches to hydrating skin, the molecular mechanisms of UV-related dehydration have not been elucidated. Water movement across the plasma membrane occurs via two pathways: diffusion and recently discovered water channels or aquaporins, or AQPs. AQPs are expressed in various epithelia and endothelia as well as in cell types that were originally thought not to carry out fluid transport. AQP3 is specifically expressed in the basal layer with a crucial role in the hydration of the epidermis. UV radiation has been shown to downregulate a number of critical extra- and intracellular proteins, leading to impaired cellular functions and eventually skin photoaging. UV also downregulates desmosomal proteins, suggesting that membrane proteins might also be the targets of destruction. However, the question whether UV radiation affects cell membrane water channel protein AQP3 expression and/or function in skin cells has yet to be addressed. One of the most studied protective agents against UV-induced photoaging is all-trans retinoic acid (atRA). Topical application of atRA enhances the repair of UV-damaged skin in vivo, leading to the effacement of wrinkles. AtRA has a significant diminishing effect on UV-induced water loss, as well as reduced wound healing. However, whether atRA affects AQP3 in human skin cells has not yet been studied. Given that UV radiation induces human skin dehydration and skin photoaging, and that AQP3 water channel plays an important role in skin physiology, we undertook this project to investigate whether UV radiation downregulates AQP3 and water movement, and whether the popular atRA or other reagents have any protective effects against UV-induced dehydration.