| Project/Area Number |
25462832
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Emergency medicine
|
|---|
| Research Institution | Teikyo University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
宮川 誠 帝京大学, 中央動物実験施設, 教務職員 (80398734)
|
|---|
| Research Collaborator |
KUROSAKI Kumiko
|
|---|
| Project Period (FY) |
2013-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 敗血症 / 腎傷害 / β２アドレナリン受容体 / グルココルチコイド / TNF-α / ヒストン / 腎機能 / ＴＮＦ－α / ヒストン修飾 / ステロイド / 遺伝子導入 / 多臓器障害 / 副腎皮質ステロイド薬 / エピジェネテイクス / 腎臓 / TNFーα |
|---|
| Outline of Final Research Achievements |
This study was undertaken to explore whether cross-talk between β2-adrenoceptor(β2-AR) and glucocorticoid may produce additive or even synergic anti-inflammatory effects, resulting in kidney protection against sepsis-induced acute kidney injury(AKI). Results demonstrated that administration of glucocorticoid in the kidney and renal cells with over-expression of β2-AR appeared to modulate renal dysfunction and inflammation following sepsis by altering cAMP-PKA, cannabinoid-1 and CD14-TLR4-TNF-α pathways. In addition, the combination therapy produced modulation of systemic nitric oxide and angiotensin II, and renal histone-modifying enzymes(HAT, HDAC, H3K9Ac）, which further suppressed renal TNF-α gene transcription. Moreover, the combination therapy improved the survival of the rats exposed to sepsis-induced AKI. From these findings, the effect of β2-AR activation on glucocorticoid actions via TNF-α pathways was a critical effector in the host defense against sepsis-induced AKI.
|
