Targeting Cytoglobin gene regulation as a promising strategy for treatment of liver fibrosis
| Project/Area Number |
15K08314
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Osaka City University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
松原 勤 大阪市立大学, 大学院医学研究科, 准教授 (20628698)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | Cytoglobin / 肝線維化 / 肝星細胞 / 抗線維化治療法 / FGF2 / 線維化 / 活性化 / 肝臓 / 繊維化 |
|---|
| Outline of Final Research Achievements |
Cytoglobin (CYGB) belongs to the mammalian globin family and is primarily localized in fibroblastic cells of various organs, including hepatic stellate cells (HSCs). In addition to its gas-binding ability, CYGB may be relevant for organ fibrosis and cancer due to its anti-oxidative properties; however, the regulation of CYGB gene expression remains unknown. We report fibroblast growth factor 2 (FGF2) as a key factor for CYGB induction in human HSCs through JNK signaling. ChIP analyses revealed the augmented binding of phospho-c-JUN to its consensus motif in the CYGB promoter, upon FGF2 stimulation. Additionally, FGF2 induced a quiescence-like phenotype of HSCs partly via the ERK pathway. In bile duct-ligated mice, FGF2 administration ameliorated liver fibrosis and significantly reduced activated HSCs. In conclusion, FGF2 triggers CYGB gene expression and deactivation of myofibroblastic human HSCs, indicating its therapeutic potential for treating liver fibrosis.
|
Report
(4 results)
Research Products
(19 results)
