Cross-Talk between Transforming Growth Factor-beta and Periostin Can Be Targeted for Pulmonary Fibrosis
| Project/Area Number |
18K08144
|
|---|
| 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 | Saga University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
出原 賢治 佐賀大学, 医学部, 教授 (00270463)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | ペリオスチン / 間質性肺炎 / 線維化 / インテグリン / TGF-beta / 肺線維症 / TGF-β |
|---|
| Outline of Final Research Achievements |
In this study, we sought to learn whether the cross-talk between TGF-b and periostin leads to generation of pulmonary fibrosis and whether inhibitors for integrin aVb3, a periostin receptor, can block pulmonary fibrosis in model mice and the TGF-b signals in fibroblasts from patients with IPF. We found that cross-talk exists between TGF-b and periostin signals via aVb3/b5 converging into Smad3. This cross-talk is necessary for the expression of TGF-b downstream effector molecules important for pulmonary fibrosis. Moreover, we identified several integrin inhibitors capable of blocking cross-talk with TGF-b signaling. One of the compounds, CP4715, attenuated bleomycin-induced pulmonary fibrosis in mice and the TGF-b signals in fibroblasts from patients with IPF. These results suggest that the cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block this cross-talk.
|
| Academic Significance and Societal Importance of the Research Achievements |
間質性肺炎の発症機序においてTGF-bの重要性が知られている。TGF-bは、静止期の線維芽細胞を筋線維芽細胞へ変換させるとともに、線維芽細胞に作用してコラーゲンなどの細胞外マトリックスタンパク質の産生を誘導し、肺線維化の形成に寄与している。しかし、生体内におけるTGF-bの活性化調節機構について未だ多くの点が不明である。また、抗TGF-b抗体のIPFに対する治療薬の治験は、副作用の問題のため中断されている。
今回、我々の同定したペリオスチン/TGF-bのクロストークの阻害ははTGF-bシグナルを全てを抑えるのではなく、特定の線維化シグナルを阻害するので、IPFの新たな治療戦略として期待される。
|
Report
(4 results)
Research Products
(4 results)
-
[Journal Article] The Crosstalk Between TGF-β and Periostin Can Be Targeted for Pulmonary Fibrosis.2020
Author(s)
Nanri Y, Nunomura S, Terasaki Y, Yoshihara T, Hirano Y, Yokosaki Y, Yamaguchi Y, Feghali- Bostwick C, Ajito K, Murakami S, Conway SJ, Izuhara K.
-
Journal Title
Am J Respir Cell Mol Biol
Volume: 62
Issue: 2
Pages: 204-216
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
