2009 Fiscal Year Final Research Report
Role of Transcriptional factors and Gene Therapy in Sepsis
| Project/Area Number |
19390405
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
MATSUDA Naoyuki Kyoto University, 医学研究科, 准教授 (50332466)
|
|---|
| Project Period (FY) |
2007 – 2009
|
| Keywords | 敗血症 / 転写因子 / nuclear factor κB / Activator protein 1 / cyclic AMP responsive element / 遺伝子治療 / Death受容体 / アポトーシス |
|---|
| Research Abstract |
This study was performed in order to analyze the function of transcription factors and the gene therapy in the pathogenesis of sepsis. Transcription factor NF-kB, AP-1 and CRE increased the activity in various major organs of septic mouse with cecal ligation and puncuture. Gene therapy using decoy oligonucleotides of the transcription factors inhibited the activity in septic mice. NF-kB induced inflammatory molecules such as chemokines and adhesion molecules in septic major organs. On the other side, AP-1 was found to be involved in increased transcription of extrinsic apoptotic signaling molecules including death receptors. Decreased AP-1 activity significantly improved survival of septic mice. However, CRE decoy oligonucleotides did not strongly linked to the transcription of inflammatory molecules and apoptosis-related molecules.
|
