Organ-specificity of lung fibroblast and its relationship to lung disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08170
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: The University of Tokyo
• Principal Investigator: Saito Akira 東京大学, 医学部附属病院, 講師 (90591412)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 線維芽細胞 / 肺線維症 / 肺癌 / 転写因子 / スーパーエンハンサー / TBX4 / FOXL1

Outline of Final Research Achievements

By comparing the gene expression profiles derived from different organs, we identified eight transcription factors that show relatively higher expression and are associated with super-enhancers (TBX2, TBX4, TBX5, HOXA5, FOXL1, FOXP1, MEIS1 and TGIF1). TBX4 functions as a master transcription factor in lung fibroblasts. TBX4 expression is downregulated by TGF-beta and is lower in lung cancer-associated fibroblasts. Highly activated FOX gene cluster (FOXL1, FOXC2 and FOXF1) is a hallmark of lung fibroblasts. FOXL1 is involved in the regulation of TAZ/YAP and BMP signaling, and its expression is higher in pulmonary fibrosis. Transcription factors unique to lung fibroblasts are involved in the pathogenesis of lung cancer or pulmonary fibrosis.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

肺組織に由来する線維芽細胞において、組織特異的に発現している遺伝子群を同定し、機能的に重要性が高いと思われる転写因子（TBX4およびFOXL1）を選定し、その生理的・病理的な役割を検討した。これらの転写因子は肺癌や肺線維症において発現変化がみられており、これらの疾患の分子病態に関与している可能性がある。