The role of Dok adaptors in pulmonary disorders

Dok 适配器在肺部疾病中的作用

• 批准号: 23591115
• 负责人: MASHIMA Ryuichi
• 金额: $ 3.24万
• 依托单位: Keio University (2013)Akita University (2012)The University of Tokyo (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591115/
• 关键词: 喘息; チロシンキナーゼ; アダプター分子; 疾患モデルマウス; 閉塞性肺疾患; アダプタータンパク質

Dok adaptor proteins play important roles on the proper regulation of tyrosine kinase-mediated signaling pathways. In this study, I particularly investigated the role of Dok adaptors in pulmonary disorders such as asthma. Although many causative factors of asthma have been suggested, dysfunction of immune cells is one of the major reason of this disease. In these immune cells, three Dok adaptors can be detected, therefore, the role of them in asthma was investigated using knockout mice.As expected, mice lacking three Dok adaptors exhibited an abnormal increase in airway hyperreactivity, a biological measure of asthma. Consistent with previous findings, the levels of Th2 cytokines in bronchoalveolar lavage fluids were also elevated in these mice. Furthermore, histological examination revealed hyperplasia of airway epithelial cells and accumulation of goblet cells. These results proved that Dok adaptor proteins play a key role on the regulation of asthma.

Dok衔接蛋白在酪氨酸激酶介导的信号通路的正确调节中起重要作用。在这项研究中，我特别研究了Dok适配器在哮喘等肺部疾病中的作用。 虽然哮喘的致病因素很多，但免疫细胞功能紊乱是其主要原因之一。 在这些免疫细胞中，可以检测到三个Dok衔接子，因此，使用敲除小鼠研究它们在哮喘中的作用。正如预期的那样，缺乏三个Dok衔接子的小鼠表现出气道高反应性的异常增加，这是哮喘的生物学指标。 与先前的发现一致，在这些小鼠中，支气管肺泡灌洗液中的Th2细胞因子水平也升高。 此外，组织学检查显示气道上皮细胞增生和杯状细胞积聚。 这些结果证明Dok衔接蛋白在哮喘的调节中起关键作用。

项目成果

Dok-1 and Dok-2 deficiency induces osteopenia via regulation of osteoclasts

Dok-1 和 Dok-2 缺乏通过调节破骨细胞诱导骨质减少

• DOI: 10.1002/jcp.22909
• 发表时间: 2011
• 期刊: J. Cell. Physiol.
• 作者: 吉岡美紗子;石丸喜朗;朝倉富子;阿部啓子;長尾遥奈，西村伸一，藤澤和謙，珠玖隆行;Aya Kawamata
• 通讯作者: Aya Kawamata