2013 Fiscal Year Final Research Report
Identification of Hic-5 as a novel molecule in the development of abdominal aortic aneurysms
| 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
|
| Keywords | 大動脈瘤 |
|---|
| 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.
|
-
-
-
-
[Journal Article] Identification of Hic-5 as a novel regulatory factor for integrin αIIbβ3 activation and platelet aggregation in mice2012
Author(s)
Kim-Kaneyama JR, Miyauchi A, Lei XF, Arita S, Mino T, Takeda N, Kou K, Eto K, Yoshida T, Miyazaki T, Shioda S, Miyazaki A
-
Journal Title
J Thromb Haemost
Volume: 10(9)
Pages: 1867-74
DOI
Peer Reviewed
-
-
-
-
-
-
-
