Functional analysis of tissue inhibitor of metalloproteinase-1 (TIMP-1) after influenza A virus infection

甲型流感病毒感染后金属蛋白酶组织抑制剂-1(TIMP-1)的功能分析

• 批准号: 24790372
• 负责人: NAKAYAMA Yosuke
• 金额: $ 2.91万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790372/
• 关键词: 感染症; インフルエンザ; TIMP-1

Matrix metalloproteinases (MMPs) and their inhibitors play an important regulatory role in the inflammatory responses and physiologic tissue remodeling. We found that the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which is a specific inhibitor of MMPs, was remarkably induced in the lungs after influenza A virus (IAV) infection. Therefore, we focused on the function of TIMP-1 for the pathogenesis, and infected TIMP-1 KO and wild type (WT) mice with the virus. After IAV infection, the survival rate of TIMP-1 KO mice was lower than that of WT mice. In addition, at 7 day after the infection, severe hemorrhagic tendency was detected in the bronchoalveolar lavage fluid (BALF) in TIMP-1 KO mice, and inflammatory cell accumulation in BALF increased in TIMP-1 KO mice, compared with WT mice. Therefore, it was suggested that TIMP-1 is involved in the protection of the lung against excessive inflammatory response.

基质金属蛋白酶（MMP）及其抑制剂在炎症反应和生理组织重塑中发挥着重要的调节作用。我们发现，甲型流感病毒（IAV）感染后，肺部显着诱导金属蛋白酶组织抑制剂-1（TIMP-1）的表达，TIMP-1是MMP的特异性抑制剂。因此，我们重点关注TIMP-1在发病机制中的功能，并用病毒感染TIMP-1 KO和野生型（WT）小鼠。 IAV感染后，TIMP-1 KO小鼠的存活率低于WT小鼠。此外，感染后第7天，TIMP-1 KO小鼠的支气管肺泡灌洗液（BALF）中检测到严重的出血倾向，并且与WT小鼠相比，TIMP-1 KO小鼠BALF中炎症细胞的积累增加。因此，有人认为TIMP-1参与保护肺部免受过度炎症反应。

项目成果

インフルエンザAウイルス感染におけるtissue inhibitor of metalloproteinase-1 (TIMP-1)の機能解析

金属蛋白酶组织抑制剂-1(TIMP-1)在甲型流感病毒感染中的功能分析

• 发表时间: 2013
• 作者: 中山洋佑;宮崎忠明
• 通讯作者: 宮崎忠明