investigation on the mechanisms of cyst formation in Birt-Hogg-Dube syndrome

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19467
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Juntendo University
• Principal Investigator: Yoshito Hoshika 順天堂大学, 医学部, 非常勤助教 (70772515)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: FLCN / 肺胞上皮細胞 / 線維芽細胞 / 中皮細胞 / 細胞外マトリックス / 自然気胸 / 肺のう胞

Outline of Final Research Achievements

We isolated type II alveolar epithelial cells (ATII) and fibroblasts from lung tissues that was resected during operation of pneumothorax in patients with Birt-Hogg-Dubé syndrome (BHDS). Additionally pleural mesothelial cells (PMC) was isolated from pleural lavage fluid that was also obtained during operation. ATII derived from BHDS showed decreased proliferation in the 3-D organoid culture system and increased apoptosis as compared with ATII obtained from normal lung tissues ( a normal part of lobectomied lung in patients with lung cancer). We performed gene expression microarray analysis using lung fibroblasts from BHDS and control and PMC from BHDS and primary spontaneous pneumothorax. We found no apparent difference in gene expression of lung fibroblasts, but significant differences in PMC regarding genes involved in migration, adhesion, wound healing and coagulation.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

遺伝的に気胸発症しやすいBHDS患者の肺構成細胞を検討したところ、ATIIと中皮細胞により強い機能や遺伝子発現の変化が認められた。非遺伝性の自然気胸や嚢胞性肺疾患の病態においても、これら2種類の細胞が重要である可能性が示唆される。気胸や嚢胞形成の病態研究における方向性を示した点に学術的意義がある。