Gonadal hormones as mediators of sex and gender influences in asthma

性腺激素作为性和性别影响哮喘的介质

基本信息

  • 批准号:
    10876655
  • 负责人:
  • 金额:
    $ 17.47万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-10 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

ABSTRACT Asthma is a lung disease caused by exaggerated lung inflammation leading to airway obstruction and compromised airflow. Despite significant advances in its diagnosis and treatment, asthma continues to be a significant health problem affecting more than 25 million patients in the US, and over 300 million around the world. Well-characterized sex and gender differences in asthma have been reported, with changes in morbidity throughout life. Starting around puberty and peaking during mid-life, women have increased asthma prevalence and higher rates of asthma exacerbations than men. Causes of these disparities remain unclear; however, studies have shown that sex-specific inflammatory mechanisms controlled by hormones contribute to differences in airway reactivity in response to environmental stimuli. Despite this, experimental models of asthma have not explored the contributions of sex hormones to inflammatory mechanisms in the female and male lung, and no studies have explored the effects of feminizing hormone therapy with estrogen in the lungs of trans women. Prior studies from our laboratory using mouse models have reported sex differences and influences of the estrous cycle and circulating sex hormones in the inflammatory response to environmental exposures. Based on these findings, we hypothesized that female sex hormones, specifically estrogens, contribute to asthma phenotypes in the lung via activation of inflammatory mechanisms mediated by estrogen receptors. In the proposed study, we will test this hypothesis by determining the mechanisms by which estrogen mediates sex and gender influences in asthma. In Aim 1, we will determine the contributions of sex chromosome complement (XX vs. XY) vs. gonadal hormones in asthma phenotypes, by developing a mouse house dust mite (HDM) asthma model on the four core genotypes (FCG) model. In Aim 2, we will study the contributions of estrogens to HDM-induced asthma outcomes using male and female gonadectomized mice treated with estradiol, as well as bronchial epithelial cells from male and female healthy and asthma patients to exposed to HDM in the presence/absence of estrogen receptor agonists/antagonists. In Aim 3, we will determine the roles of nuclear (ER) and membrane- bound (GPER-1) estrogen receptors in estrogen-mediated mechanisms of inflammation in HDM-induced asthma, using ER and GPER1 knockout mice. Our studies will be the first to characterize estrogen-mediated mechanisms of inflammation in asthma phenotypes in the male and female lung, contributing to the characterization of sex- and gender-specific factors accounting for inter-individual differences, as well as the effects of feminizing hormone therapy in lung pathobiology. We expect that our studies would serve to develop potential sex- and gender-specific treatments and recommendations for dosage of therapeutic agents to treat and prevent asthma in cis and transgender women.
摘要 哮喘是一种肺部疾病,由过度的肺部炎症导致气道阻塞, 气流受损尽管在诊断和治疗方面取得了重大进展,但哮喘仍然是一个严重的疾病。 严重的健康问题影响了美国2500多万患者, 世界据报道,哮喘的性别和性别差异具有很好的特征,发病率也有变化 在生活中。从青春期开始,到中年达到高峰,女性哮喘患病率增加 哮喘恶化的比率也高于男性。造成这些差异的原因尚不清楚;然而, 研究表明,由激素控制的性别特异性炎症机制有助于差异 气道对环境刺激的反应性。尽管如此,哮喘的实验模型并没有 探索了性激素对女性和男性肺部炎症机制的作用, 研究已经探索了在变性妇女的肺中使用雌激素的女性化激素治疗的效果。之前 我们实验室使用小鼠模型的研究报告了性别差异和发情的影响, 循环和循环性激素在炎症反应的环境暴露。基于这些 研究发现,我们假设女性性激素,特别是雌激素,有助于哮喘表型 通过激活雌激素受体介导的炎症机制在肺中发生。在拟议的研究中, 我们将通过确定雌激素介导性和性别的机制来检验这一假设 哮喘的影响。在目标1中,我们将确定性染色体补体的贡献(XX与XY) vs.性激素在哮喘表型中的作用,通过建立小鼠屋尘螨哮喘模型, 四核心基因型(FCG)模型。在目标2中,我们将研究雌激素对HDM诱导的 使用雌二醇治疗的雄性和雌性性腺切除小鼠的哮喘结果,以及支气管 来自男性和女性健康和哮喘患者的上皮细胞在存在/不存在HDM的情况下暴露于HDM 雌激素受体激动剂/拮抗剂。在目标3中,我们将确定核(ER)和膜的作用- 结合(GPER-1)雌激素受体在HDM诱导的雌激素介导的炎症机制中的作用 哮喘,使用ER和GPER 1敲除小鼠。我们的研究将是第一个描述雌激素介导的 男性和女性肺中哮喘表型的炎症机制,有助于 说明个体间差异的性别和性别特异性因素的特征,以及 女性化激素治疗在肺病理学中的作用。我们希望我们的研究能有助于发展 潜在的性别和性别特异性治疗以及治疗药物剂量的建议 预防顺性和变性女性的哮喘。

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sex Differences in Airway Remodeling and Inflammation: Clinical and Biological Factors.
  • DOI:
    10.3389/falgy.2022.875295
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ekpruke, Carolyn Damilola;Silveyra, Patricia
  • 通讯作者:
    Silveyra, Patricia
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Patricia Silveyra其他文献

Patricia Silveyra的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Patricia Silveyra', 18)}}的其他基金

Gonadal hormones as mediators of sex and gender influences in asthma
性腺激素作为性和性别影响哮喘的介质
  • 批准号:
    10580911
  • 财政年份:
    2022
  • 资助金额:
    $ 17.47万
  • 项目类别:
Promoting DEIA in Lung Disease Research Through a Mentored Training Experience at IUB-SPH
通过 IUB-SPH 的指导培训经验促进 DEIA 在肺部疾病研究中的应用
  • 批准号:
    10792180
  • 财政年份:
    2021
  • 资助金额:
    $ 17.47万
  • 项目类别:
Gonadal hormones as mediators of sex and gender influences in asthma
性腺激素作为性和性别影响哮喘的介质
  • 批准号:
    10448428
  • 财政年份:
    2021
  • 资助金额:
    $ 17.47万
  • 项目类别:
Gonadal hormones as mediators of sex and gender influences in asthma
性腺激素作为性和性别影响哮喘的介质
  • 批准号:
    10308138
  • 财政年份:
    2021
  • 资助金额:
    $ 17.47万
  • 项目类别:
Gonadal hormones as mediators of sex and gender influences in asthma
性腺激素作为性和性别影响哮喘的介质
  • 批准号:
    10653080
  • 财政年份:
    2021
  • 资助金额:
    $ 17.47万
  • 项目类别:
Sex-specific mechanisms of ozone-induced acute lung inflammation
臭氧引起的急性肺部炎症的性别特异性机制
  • 批准号:
    9316707
  • 财政年份:
    2016
  • 资助金额:
    $ 17.47万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 17.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了