Gender-specific role of GPR30 estrogen receptors in controlling gastrointestinal functions.

GPR30 雌激素受体在控制胃肠功能中的性别特异性作用。

• 批准号: 290740556
• 负责人: Privatdozent Dr. Andrei Sibaev
• 金额: --
• 依托单位: Medizinische Klinik und Poliklinik II - Großhadern
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/290740556?language=en
• 关键词: Gender; specific; role; GPR30; estrogen

Functional gastrointestinal disorders are frequent reasons for patients to seek medical help and are associated with impaired quality of life. Prevalences of dyspepsia and irritable bowel syndrome ranges from 10 to 15 %. Drug treatment options of these functional disorders are limited and mostly consist of different symptomatic therapeutic approaches. Interestingly functional gastrointestinal disorders are more frequent in females, at least females more frequently seek medical advice.The GPR30 receptor is a recently reported receptor which was shown to be a possible target for estrogens. Localisation and function of this receptor are unknown. The suggested project wants to investigate whether GPR30 receptors are localized in the gastrointestinal tract and if so, to identify the functional meaning of these receptors. Our translational approach comprises studies in human tissue and for more sophisticated characterisation we will employ mice. Employing PCR and immunohistochemistry we aim to localize GPR 30 in the gastrointestinal tract followed by in vitro pharmacological and electrophysiological experiments that will allow us to comment on the possible functional relevance of GPR30 in the control of gastrointestinal function. Building on these experiments we intend to perform experiments in in vivo models mimicking symptoms of irritable bowel syndrome in order to identify possible GPR30 actions on gastrointestinal motility, diarrhoea, visceral sensation and inflammation. An important overarching aim is to identify possible gender differences in GPR30 expression or function. In summary the project intends to explore the role of GPR30 in the control of gastrointestinal function and to characterize whether GPR30 is a suitable target for future treatment of functional gastrointestinal disorders.

功能性胃肠道疾病是患者寻求医疗帮助的常见原因，并与生活质量受损有关。消化不良和肠易激综合征的患病率从10%到15%不等。这些功能性疾病的药物治疗选择有限，主要包括不同的对症治疗方法。有趣的是，功能性胃肠道疾病在女性中更常见，至少女性更频繁地寻求医疗建议。GPR30受体是最近报道的一种受体，被证明是雌激素的可能靶点。该受体的定位和功能尚不清楚。这个建议的项目想要调查GPR30受体是否定位于胃肠道，如果是的话，确定这些受体的功能意义。我们的翻译方法包括对人体组织的研究，为了更复杂的特征，我们将使用老鼠。利用聚合酶链式反应和免疫组织化学的方法，我们的目标是在胃肠道定位GPR30，然后进行体外药理和电生理实验，以评价GPR30在胃肠功能控制中可能的功能相关性。在这些实验的基础上，我们打算在模拟肠易激综合征症状的活体模型上进行实验，以确定GPR30对胃肠动力、腹泻、内脏感觉和炎症可能的作用。一个重要的首要目标是确定GPR30在表达或功能上可能存在的性别差异。综上所述，该项目旨在探索GPR30在胃肠功能控制中的作用，并确定GPR30是否为未来治疗功能性胃肠疾病的合适靶点。

项目成果

FABP4 blocker attenuates colonic hypomotility and modulates white adipose tissue‐derived hormone levels in mouse models mimicking constipation‐predominant IBS

• DOI: 10.1111/nmo.13272
• 发表时间: 2018-05
• 期刊: Neurogastroenterology & Motility
• 影响因子: 3.5
• 作者: P. Mosińska;D. Jacenik;M. Sałaga;A. Wasilewski;A. Cygankiewicz;A. Sibaev;A. Mokrowiecka;Ewa Małecka-Panas;I. Pintelon;Martin Storr;Jean-Pierre Timmermans;Wanda M. Krajewska;J. Fichna