Study on the germline FLCN mutations and the mechanism of pulmonary cyst formation in Birt-Hogg-Dube syndrome

Birt-Hogg-Dube综合征种系FLCN突变及肺囊肿形成机制研究

• 批准号: 22790767
• 负责人: KIKKAWA Mika
• 金额: $ 2.5万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790767/
• 关键词: Birt-Hogg-Dube症候群(BHD症候群); 嚢胞性肺疾患; 気胸; 遺伝子検査; フォリキュリン(Folliculin/FLCN); BHD症候群; 肺線維芽細胞; 肺嚢胞

In order to understand the mechanism of pulmonary cyst formation in Birt-Hogg-Dube(BHD) syndrome, I examined the germline FLCN mutation in patients with BHDS and functional assay of lung fibroblasts isolated from patients with BHDS. Germline FLCN mutations I identified distributed all exons of the FLCN gene, but four mutations were frequently demonstrated in our Japanese BHDS patients. Genotype-phenotype correlation is currently under investigation. As for functional analysis of BHDS lung fibroblasts, I examined proliferation and the ability of migration and gel contraction. As compared with human fetal lung fibroblasts(HFL), lung fibroblasts from BHDS showed decreased migration toward fibronectin while proliferation and gel contraction ability was similar to those with HFL. In addition, the expression of TGF beta 1, fibronectin, type I collagen was decreased in BHDS lung fibroblasts when determined by real-time PCR.

为了了解Birt-Hogg-Dube（BHD）综合征肺囊肿形成的机制，我检查了BHDS患者的种系FLCN突变以及从BHDS患者分离的肺成纤维细胞的功能分析。我发现种系 FLCN 突变分布在 FLCN 基因的所有外显子中，但在我们的日本 BHDS 患者中经常发现四种突变。基因型-表型相关性目前正在研究中。至于BHDS肺成纤维细胞的功能分析，我检查了增殖以及迁移和凝胶收缩的能力。与人胎儿肺成纤维细胞（HFL）相比，来自BHDS的肺成纤维细胞向纤连蛋白的迁移减少，而增殖和凝胶收缩能力与HFL相似。此外，通过实时PCR测定，BHDS肺成纤维细胞中TGFβ1、纤连蛋白、I型胶原的表达降低。

项目成果

気胸・肺嚢胞スタディグループ

气胸/肺囊肿研究组

FLCN mutation and clinical manifestations of patients with Birt-Hogg-Dube syndrome whose presenting feature was pnuemothrax and/or multiple lung cysts

以气胸和/或多发性肺囊肿为特征的 Birt-Hogg-Dube 综合征患者 FLCN 突变与临床表现

• 发表时间: 2011
• 作者: Kunogi;M.;Kurihara;M.;Shigihara Ikegami;T.;Kobayashi;T.;Shindo;N.;Kumasaka;T.;Gunji;Y.;Kikkawa;M.;Iwakami;S.;Hino;O.;Takahashi;K.;Seyama;K.;吉川美加
• 通讯作者: 吉川美加