ADAM33 gene and environment interactions in developing lungs and their involvement in the early life origin of asthma

ADAM33 基因和环境在肺部发育中的相互作用及其与哮喘早期生命起源的关系

• 批准号: G0802804/1
• 负责人: Hans Haitchi
• 金额: $ 131.9万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802804%2F1
• 关键词: ADAM33; gene; environment; interactions; developing

Asthma is a common disease affecting both adults and children. It causes wheeziness, chesttightness and cough and is often triggered by exposure to allergens (eg. dust or animal fur). As aresult, the airways contract too much and too easily, limiting airflow into the lung. Asthma tends torun in families suggesting there are ‘asthma’ genes. ADAM33 is such a gene where small changeshave been found in people with asthma and in young children at risk of asthma. It is found inspecialized airway ‘smooth muscle’ cells (ASMCs) that cause airway ‘twitchiness’ in asthma and it isreleased in fluid that is present in the airways of asthmatic patients. In baby lungs, I have foundthat ADAM33 occurs in stem cells that give rise to ASMCs. Therefore, the objectives of my researchare to study the role of ADAM33 in airway development and to understand whether release ofADAM33 can give rise to abnormal ASMC development that might lead to asthma. I will alsoinvestigate whether, and how maternal allergy, a factor that predisposes babies for asthma, affectsADAM33 in ASMC. These studies should help devise new treatments for asthma close to the origin ofthe disease.

哮喘是一种常见的疾病，影响成人和儿童。它会引起喘息、胸闷和咳嗽，通常是由接触过敏原（如过敏原）引发的。灰尘或动物皮毛）。因此，气道收缩太多太容易，限制了进入肺部的气流。哮喘倾向于在家族中发生，这表明存在“哮喘”基因。ADAM33就是这样一个基因，在哮喘患者和有哮喘风险的幼儿中发现了微小的变化。它被发现存在于导致哮喘患者气道“抽搐”的特化气道“平滑肌”细胞（ASMCs）中，并在哮喘患者气道中的液体中释放。在婴儿肺中，我发现ADAM33存在于产生ASMC的干细胞中。因此，本研究的目的是研究ADAM33在气道发育中的作用，并了解ADAM33的释放是否会引起ASMC的异常发育，从而可能导致哮喘。我还将调查母体过敏是否以及如何影响ASMC中的ADAM 33，母体过敏是婴儿哮喘的易感因素。这些研究应该有助于设计出接近哮喘起源的新疗法。