CELL SIGNALING LEADING TO UV-INDUCED CELL INJURY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 长期暴露在紫外线辐射下会产生皱纹。皮肤暴露在紫外线下后，皮肤的水分含量和保水能力往往会下降，导致皱纹和延迟伤口愈合等有害影响。虽然化妆品面膜仍然是最受欢迎的保湿皮肤方法之一，但紫外线相关脱水的分子机制尚未阐明。水在质膜上的移动通过两条途径发生：扩散和最近发现的水通道或水通道，或水通道，或水通道蛋白。水通道蛋白在各种上皮和内皮细胞以及最初被认为不进行液体运输的细胞类型中都有表达。AQP3在基底层特异表达，在表皮水合过程中起着至关重要的作用。紫外线辐射已被证明下调了一些关键的细胞外和细胞内蛋白质，导致细胞功能受损，最终导致皮肤光老化。紫外线还下调桥粒蛋白的表达，这表明膜蛋白也可能是破坏的目标。然而，紫外线辐射是否影响皮肤细胞膜水通道蛋白AQP3的表达和/或功能的问题尚未得到解决。全反式维甲酸(AtRA)是研究最多的抗紫外光老化的保护剂之一。局部应用全反式维甲酸可促进体内紫外线损伤皮肤的修复，从而消除皱纹。全反式维甲酸对紫外线引起的水分丢失有显著的减少作用，并降低了伤口愈合。然而，全反式维甲酸是否影响人皮肤细胞中的AQP3还没有研究。鉴于紫外线辐射导致人体皮肤脱水和皮肤光老化，而AQP3水通道在皮肤生理中起重要作用，我们开展了这一项目，以研究紫外线辐射是否下调AQP3和水分运动，以及流行的atRA或其他试剂是否对紫外线诱导的脱水具有保护作用。

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.