| Project/Area Number |
17H04215
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Collagenous pathology/Allergology
|
|---|
| Research Institution | Kochi University |
|---|
Principal Investigator |
Naka Tetsuji 高知大学, 教育研究部医療学系臨床医学部門, 教授 (30303936)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
藤本 穣 高知大学, 教育研究部医療学系臨床医学部門, 准教授 (00379190)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
|
|---|
| Keywords | リウマチ学 / 難病 / 免疫学 / シグナル伝達 |
|---|
| Outline of Final Research Achievements |
By proteomics-based strategy, we previously identified LRG as a promising serum biomarker for inflammation. Recent studies highlighted LRG as a functional protein presumably involved in the regulation of TGFβ signals. In this study, by using both LRG-deficient mice and wild-type mice, we generated animal models of rheumatic diseases (autoimmune arthritis and pulmonary fibrosis) in order to perform functional analysis of LRG. LRG deficiency in mice resulted in the alleviation of joint damage and pulmonary fibrosis, accompanied by reduced activation of TGFβ signal. This study revealed that LRG is a molecule involved in the pathogenesis of rheumatic diseases by enhancing TGFβ signal and is a potential therapeutic target for these diseases.
|
| Academic Significance and Societal Importance of the Research Achievements |
多彩な病態生理学的活性をもつTGF-βは、難治性疾患の治療標的として以前から注目されている。しかしTGF-β欠損マウスは致死であり、TGF-β自身を強力に阻害する治療薬には副作用の懸念が大きい。今回の研究によってLRGがリウマチ疾患の病態形成に関わる分子であること、さらにLRG阻害によってTGF-βが有する病態促進作用を軽減できる可能性を示すことが出来た。LRG欠損マウスは健康に発育するため、阻害時の副作用の問題が少ないと期待される。LRGは難治性リウマチ疾患の治療標的として有望であり、阻害戦略の確立が今後の課題である。
|
