The Lipid and Tight Junction Epidermal Barriers are Interdependent

脂质和紧密连接表皮屏障是相互依赖的

• 批准号: 8384822
• 负责人: Theodora M Mauro
• 金额: $ 20.01万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8384822
• 关键词: Air; Animal Model; Bacteria; Bacterial Infections; Birth; Clinical; Competence; Data; Development; Environment; Epidermis; Epithelium; Fetal Development; Future; Human; Infectious Skin Diseases; Invaded; Ions; Knowledge; Laboratory Study; Lifting; Lipids; Modeling; Neonatal; Organism; Perinatal; Permeability; Play; Pregnancy; Premature Infant; Proteins; Rattus; Research; Risk; Role; Sepsis; Skin; Staphylococcus aureus; Stratum corneum; Testing; Tight Junctions; Toxin; Water; Work; base; clinical practice; fetal; improved; in utero; novel strategies; postnatal; premature; prenatal; prevent; research study; response; secretion process

DESCRIPTION (provided by applicant): Hypothesis: Prior studies have shown that tight junctions (TJ) proteins are critical for epidermal permeability barrier formation in utero, but the function of TJ and their constituent proteins in postnatal epidermis is unknown. We find that the expression and function of mammalian epidermal TJ change during epidermal development. Therefore, we hypothesize that the TJ and stratum corneum lipid barriers subserve different functions, but are interdependent. Description of proposed work: Our most recent research suggests that TJ and the stratum corneum barrier formed by lipid secretion and processing serve complementary roles in epidermal permeability development. We find that water-impermeant TJ, similar to those in other tight epithelia, are formed first during epidermal development, but these TJ lose their ability to block water and ions as the lipid barrier is formed In this R21 proposal, we will test whether epidermal TJ expression is modified in response to lipid barrier function. Aim #1 will assess how changes in the lipid barrier control TJ expression and function in prenatal and perinatal epidermal development. Aim #2 will test whether TJ expression protects the epidermis from Staphylococcus aureus (SA) invasion. These experiments will form the basis for a later R01 proposal Impact: While many laboratories are studying TJ or the lipid barrier in the epidermis, to date no studies have focused on the relationship between these complementary barriers. Moreover, the relationship between these barriers may have a profound effect on the ability of prenatal, premature, and neonatal skin to resist bacterial infection. Thus, this research is likely to exert a sustained, powerful influence n the research studying epidermal development and responses to bacterial infection. PUBLIC HEALTH RELEVANCE: This project examines the roles of tight junctions and the skin lipid barrier, two different types of barriers that we hypothesize coordinate to form an effective barrier to water, toxins and bacteria as the skin develops. Skin must change its barrier functions as it goes from being exposed to a water based environment in utero to an air-based environment after birth. Premature infants do not have fully developed barriers and therefore are at risk for serious skin infections. Findings from this project will be directly applicable to understanding and treating the critical clinical problem posed by the impaired barrier of premature infants, particularly those that are less than 33 weeks gestation. If the aims of this project are achieved, scientific knowledge will be improved by defining the relationship between the TJ and lipid epidermal barriers. Clinical practice will be improved, as novel approaches to prevent bacterial invasion of the epidermis and sepsis will be developed.

描述（由申请人提供）：假设：先前的研究表明，紧密连接（TJ）蛋白对子宫内表皮通透性屏障的形成至关重要，但 TJ及其组成蛋白在出生后表皮中的功能尚不清楚。我们发现哺乳动物表皮TJ的表达和功能在表皮发育过程中发生变化。因此，我们假设TJ和角质层脂质屏障具有不同的功能，但相互依赖。拟议工作说明：我们最近的研究表明，TJ和角质层屏障形成的脂质分泌和加工在表皮通透性的发展中发挥互补作用。我们发现，不透水的TJ，类似于那些在其他紧密的上皮细胞，在表皮发育过程中形成的第一，但这些TJ失去了他们的能力，阻止水和离子的脂质屏障的形成。在这个R21的建议，我们将测试是否表皮TJ的表达修改脂质屏障功能。目的#1将评估脂质屏障的变化如何控制TJ在产前和围产期表皮发育中的表达和功能。目的#2将测试TJ表达是否保护表皮免受金黄色葡萄球菌（SA）侵袭。这些实验将成为后来R01提案的基础影响：虽然许多实验室正在研究TJ或表皮中的脂质屏障，但迄今为止还没有研究关注这些互补屏障之间的关系。此外，这些屏障之间的关系可能对产前、早产儿和新生儿皮肤抵抗细菌感染的能力产生深远影响。因此，这项研究可能会对研究表皮发育和细菌感染反应的研究产生持续的，强大的影响。 公共卫生相关性：该项目研究了紧密连接和皮肤脂质屏障的作用，我们假设这两种不同类型的屏障在皮肤发育过程中协调形成对水，毒素和细菌的有效屏障。皮肤必须改变其屏障功能，因为它从子宫内暴露于基于水的环境到出生后暴露于基于空气的环境。早产儿没有完全发育的屏障，因此有严重皮肤感染的风险。该项目的研究结果将直接适用于理解和治疗早产儿屏障受损所带来的关键临床问题，特别是那些小于33周妊娠的早产儿。如果本项目的目标得以实现，将通过定义TJ和脂质表皮屏障之间的关系来提高科学知识。临床实践将得到改善，因为新的方法，以防止细菌入侵的表皮和败血症将被开发。