| Project/Area Number |
13671111
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
YUZAWA Yukio Nagoya University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (00191479)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KADOMATSU Kenji Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80204519)
MATSUO Seiichi Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70190410)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
|---|
| Keywords | Midkine / tubulointerstitial injury / glomerular injury / antisense ODN / knockout mouse / coagulatio-fibrynolysis / Th1 / Th2 / midkine / ヘパリン結合型成長因子 / ケモカイン |
|---|
| Research Abstract |
Midkine (MK) is a mutepotentioal heparin-binding growth factor with migration-promoting activity for neutrophils, macrophages and neurons. Although MK expression is mainly limited in the course of nephrogenesis, the enhanced expression of MK is also observed in the tubular epithelial cells in the diseased kidney. The role of MK in tubulointerstitial injuries as well as in glomerular injuries was studies. MK induces the chemotaxis of inflammatory leukocytes into the tubulointerstitium at least partially through the induction of MCP-I and MIP-2, and that MK contributes the aggravation of ischemia-induced tubulointerstitial damage.
MK anti-sense oligonucleotide (ODN) distributes in the proximal tubular epithelial cells, which is the main part for de novo MK expression, after intravenous injection, and significantly reduced the expression of MK in the tubules. Consequently, MK antisense ODN successfully block the ischemic reperfusion injuries in the tubulointerstitium.
These results strongly suggest that MK antisense ODN appears to be a candidate for the novel therapeutic approaches in ischemia-induced tubulointerstitial injuries.
|
