CELL SIGNALING LEADING TO UV-INDUCED CELL INJURY

导致紫外线引起的细胞损伤的细胞信号传导

• 批准号: 7725144
• 负责人: YINSHENG WAN
• 金额: $ 6.22万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725144
• 关键词: Address; Affect; Cell membrane; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; Cosmetics; Dehydration; Diffusion; Endothelium; Epidermis; Epithelium; Exposure to; Face; Funding; Grant; Human; Hydration status; Impaired wound healing; Institution; Liquid substance; Masks; Membrane Proteins; Molecular; Numbers; Pathway interactions; Play; Protective Agents; Proteins; Reagent; Research; Research Personnel; Resources; Role; Signal Transduction; Skin; Skin Aging; Skin Physiology; Source; Stratum Basale; Thinking; Topical application; Tretinoin; UV induced; Ultraviolet Rays; United States National Institutes of Health; Water; Water Movements; Wound Healing; aquaporin 3; cell injury; cell type; extracellular; in vivo; protective effect; repaired; ultraviolet damage; water channel

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 长期暴露在紫外线辐射下会导致皱纹。皮肤的含水量和持水能力在暴露于紫外线后通常会下降，导致有害影响，如皱纹和伤口愈合延迟。虽然化妆品面膜仍然是最流行的皮肤保湿方法之一，但紫外线相关脱水的分子机制尚未阐明。水穿过质膜的运动通过两种途径发生：扩散和最近发现的水通道或水通道蛋白或AQPs。AQP在各种上皮和内皮细胞以及最初被认为不进行液体转运的细胞类型中表达。AQP 3特异性表达于基底层，在表皮的水合作用中起关键作用。 紫外线辐射已被证明会下调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。紫外线也下调桥粒蛋白，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AQP 3的表达和/或功能的问题还有待解决。全反式维甲酸（all-transretinoicacid，atRA）是研究最多的抗紫外线光老化的保护剂之一。局部应用atRA可增强体内UV损伤皮肤的修复，从而消除皱纹。AtRA对UV诱导的水分流失以及减少的伤口愈合具有显著的减少作用。然而，atRA是否影响人体皮肤细胞中的AQP 3尚未研究。鉴于紫外线辐射可诱导人体皮肤脱水和皮肤光老化，而AQP 3水通道在皮肤生理学中起着重要作用，我们开展了本项目，以研究紫外线辐射是否下调AQP 3和水运动，以及流行的atRA或其他试剂是否对紫外线诱导的脱水有任何保护作用。