| Project/Area Number |
19K07862
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52010:General internal medicine-related
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Ishii Masaki 東京大学, 医学部附属病院, 講師 (20724438)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
山口 泰弘 自治医科大学, 医学部, 教授 (60376473)
|
|---|
| Project Period (FY) |
2019-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 肺気腫 / LTBP-4 / LTBP4 / 抗炎症作用 / 抗酸化作用 / エラスチン / MMP / 肺弾性収縮能 / COPD / 炎症 / 老化 / 肺 |
|---|
| Outline of Research at the Start |
COPD は、加齢に伴い進行し高齢者に多い呼吸器疾患である。COPDの特徴的表現型である肺気腫の原因遺伝子の一つとして、Latent transforming growth factor beta binding protein 4（LTBP4）が知られているが、ヒト肺組織や肺線維芽細胞を用いた肺気腫モデルとして、喫煙暴露や遺伝子発現抑制によるLTBP4の発現低下が、肺にどのような影響を与えるかはこれまで検討が行われていないため、本研究では、肺におけるLTBP4の抗炎症・抗老化効果を中心に検証する予定である。
|
| Outline of Final Research Achievements |
LTBP4 belongs to the LTBP family of proteins and plays an important role as a structural component of extracellular matrix. LTBP4-related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema and other evidence of a generalized connective tissue disorder as the age-related disease. However, the role of LTBP4 remains unclear in the pathogenesis of emphysema.
RT-PCR analysis showed that the decreased expression of elastin and increased expression of TNF-α, MMP and TIMP-1 were observed in human lung fibroblast cells by siRNA treatment. The cell contraction assay demonstrated the decreased level of elasticity and the increase of SAβ-gal staining of cells were observed. The shotgun proteomics and RT-PCR showed that the oxidoreductases such as SOD and GSTM3 were decreased in the treatment LTBP4 siRNA by using exosome of cell culture supernatant.
|
| Academic Significance and Societal Importance of the Research Achievements |
LTBP-4はelastinによる肺弾性線維形成や肺弾性収縮力の維持に必要であるほか、ミトコンドリア機能保持を介した抗炎症・抗酸化効果、抗老化の役割を担い、肺気腫進展予防も含めた肺組織再生の上で、重要な因子である可能性が示唆された。
|
