| Project/Area Number |
24791396
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 大動脈瘤 / 腹部大動脈瘤 / 平滑筋細胞 / Hic-5 / 活性酸素種 / 細胞接着斑 |
|---|
| Research Abstract |
Reactive oxygen species (ROS) play a key role in the pathogenesis of abdominal aortic aneurysm (AAA).However, the precise mechanism of cellular signaling by ROS in the pathogenesis of AAA has not been fully elucidated.Hydrogen peroxide-inducible clone 5 (Hic-5) was identified as a H2O2 and TGFbeta-inducible gene. Using the AngII-induced AAA mice model, we showed that Hic-5-/- mice were completely protected from AAA formation.Hic-5-/- mice show decreased elastic lamina degradation, aortic expansion and rupture. Mechanistic studies showed that Hic-5 interacts as a scaffold protein specifically with JNK2 and its upstream MKK4, resulting in the phosphorylation of JNK2 and consequent MMP2 expression. Hic-5 serves as a scaffold protein specifically for activating the JNK2 pathway, thereby leading to the induction and activation of MMPs in SMCs and subsequent AAA formation.Thus, Hic-5-targeted therapy may provide a novel therapeutic option for the treatment of AAA in the future.
|
