AGING EFFECTS ON TRANSVAGINAL TRANSPORT

老化对经阴道运输的影响

• 批准号: 2878883
• 负责人: GEORGE I GORODESKI
• 金额: $ 10万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2878883
• 关键词: age difference; aging; biological fluid transport; cervix; clinical research; electrophysiology; estrogens; female; fluorescence microscopy; genital secretion; human subject; intercellular connection; microfilaments; mucus; nitric oxide; postmenopause; tissue /cell culture; vagina; women's health

DESCRIPTION: Our broad, long-term objective is to understand the mechanisms that regulate movement of fluid and solutes across the woman's reproductive tract epithelium. Our main objective in the present study is to understand how aging in women leads to decreased production of cervical mucus and vaginal fluid. We will utilize a new method that the PI has developed to culture human cervical and cervico/vaginal epithelial cells on filters, and we propose to test four hypotheses: A. That aging is associated with decreased paracellular permeability of the cervical and vaginal epithelia to transport of fluids and solutes, which leads to decreased fluid secretion. B. That aging shifts the steady-state equilibrium of action filaments in cervical and vaginal epithelial cells towards F-actin filaments in cervical and vaginal epithelial cells towards F-actin filaments in cervical and vaginal epithelial cells towards F-actin filaments in cervical and vaginal epithelial cells towards F-actin; this produces a rigid cytoskeleton which does not allow the cells to contract in response to stimuli and to increase the volume of the intercellular space, this, decreasing the paracellular permeability. Estrogen, in contrast to aging, shifts the equilibrium towards G-actin, thus producing a more dynamic cytoskeleton. C. That human cervical and vaginal cells produce nitric oxide (NO), and that NO can inhibit actin polymerization and increase paracellular permeability. D. That in human cervical and vaginal cells, estrogen increase production of NO by up-regulation of calcium-dependent NO-synthase(ecNOS). Methods will include flux and electrophysiological studies bone in a modified diffusion/Ussing chamber, fluorescence microscopy of attached cells for determinations of changes in cell size, biochemical and molecular biology microscopy of attached cells for determinations of changes in cell zie, biochemical and molecular biology assays. The present study may provide novel information on age-and estrogen-related effects on cervical-and vaginal-cell function. Health relatedness of the project: the knowledge gained in present study may be important for understanding mechanisms of disease in the cervix e.g. infertility ("cervical factor"), and conditions of excessive or diminished secretion of cervical mucus and vaginal fluid. Understanding mechanisms and regulation of cervical mucus production is important for developing compounds to alter cervical mucus characteristics. These data may improve our understanding of estrogen replacement to postmenopausal women. They may also provide efficient and simple modalities for birth control by targeting known mechanisms of transcervical and transport.

描述：我们广泛的，长期的目标是了解 调节液体和溶质在女性体内运动的机制 生殖道上皮本研究的主要目的是 了解女性衰老如何导致宫颈分泌物减少 粘液和阴道分泌物我们将使用PI拥有的新方法 开发用于培养人宫颈和宫颈/阴道上皮细胞 我们提出了四个假设：A.老化是 与宫颈细胞旁通透性降低相关， 阴道上皮细胞运输液体和溶质，这导致 液体分泌减少。B。衰老改变了 宫颈和阴道上皮细胞中的作用丝平衡 子宫颈和阴道上皮细胞中的F-肌动蛋白丝 子宫颈和阴道上皮细胞中的F-肌动蛋白丝朝向F-肌动蛋白 子宫颈和阴道上皮细胞中的细丝朝向F-肌动蛋白;这 产生一种坚硬的细胞骨架， 以响应刺激并增加细胞间的体积， 空间，这，降低细胞旁的渗透性。雌激素，在 与衰老相反，将平衡转向G-肌动蛋白，从而产生 更有活力的细胞骨架C.人类的子宫颈和阴道细胞 产生一氧化氮（NO），NO可抑制肌动蛋白聚合 并增加细胞旁渗透性。D.在人类宫颈和 阴道细胞，雌激素通过上调 钙依赖性一氧化氮合酶（ecNOS）。方法将包括通量和 电生理学在改良的扩散/尤辛室中研究骨， 用荧光显微镜检查附着的细胞， 细胞大小、附着细胞的生物化学和分子生物学显微镜检查 用于测定细胞活性、生物化学和分子生物学的变化 生物学分析目前的研究可能会提供新的信息， 雌激素对宫颈和阴道细胞功能的相关影响。健康 项目的相关性：本研究中获得的知识可能 对于了解宫颈疾病的机制很重要，例如 不孕症（“宫颈因素”），以及过度或减少 宫颈粘液和阴道液的分泌。理解机制 调节宫颈粘液的产生对于发展 化合物以改变宫颈粘液特性。这些数据可能会改善 我们对绝经后妇女雌激素替代疗法的理解。他们 还可以提供有效和简单的节育方式， 针对已知的转运和运输机制。

项目成果

Activation of P2X(7)-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice.

• DOI: 10.1186/1471-2407-9-114
• 发表时间: 2009-04-20
• 期刊: BMC cancer
• 影响因子: 3.8
• 作者: Fu W;McCormick T;Qi X;Luo L;Zhou L;Li X;Wang BC;Gibbons HE;Abdul-Karim FW;Gorodeski GI
• 通讯作者: Gorodeski GI