Investigation of the mechanism of glomerular capillary homeostasis by means of autophagy KO in endothelial cells
| Project/Area Number |
26893137
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
Tomoko Namba 大阪大学, 医学部附属病院, 医員 (30734420)
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | オートファジー / 糸球体内皮細胞 / 酸化ストレス / ミトコンドリア / 糸球体硬化 |
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| Outline of Final Research Achievements |
To investigate the role of Autophagy in vascular endothelial cells, we generated the vascular endothelial cell-specific Autophagy deficient mouse (KO mouse). KO mice had an abnormality in only glomerular capillary endothelial cells. At 4-week-old reactive oxygen species started to accumulate and, at 8-week-old double contour and accumulation of mesangial matrix were observed in the glomerulus of KO mouse. We conducted bone marrow transplantation because KO mouse died of anemia at 9-week-old. One-year-old KO mouse presented renal dysfunction and small amount of urine protein with glomerular sclerosis and interstitial fibrosis. Our in vitro study using human glomerular endothelial cells showed that siRNA-mediated knockdown of Atg5, which is involved in autophagic vesicle formation brought about endothelial dysfunction and resultant lowered survival rate. In conclusion, our data suggested that endothelial autophagy is essential for the integrity of the glomerular capillaries.
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Report
(3 results)
Research Products
(2 results)
