| Project/Area Number |
19K21395
|
|---|
| Project/Area Number (Other) |
18H06308 (2018)
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
|---|
| Review Section |
0907:Oral science and related fields
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
Lu Shiou-Ling 大阪大学, 歯学研究科, 助教 (80830083)
|
|---|
| Project Period (FY) |
2018-08-24 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | 内皮細胞 / VEGF / 化膿レンサ球菌 / Group A Streptococcus / Endothelial cell / TFEB / Autophagy / Bacteria / vegf / endothelial cell / Group A streptococcus |
|---|
| Outline of Research at the Start |
Group A streptococcus is deleterious pathogenic bacteria that causes life-threatening bacteremia through breakdown with blood vessel barrier. I had reported that in the vascular endothelial cells, GAS evades autophagy leading to it survival/replication. Here, I aim to explore a strategy for endothelial cells defense against intracellular GAS. I had found that vascular endothelial growth factor (VEGF), a general existed protein in vessel, enhanced endosomal/lysosomal degradation. I will fine the mechanism that VEGF mediates an antimicrobial effect for endothelium to against bacteria.
|
| Outline of Final Research Achievements |
Group A streptococcus (GAS) is deleterious bacteria that causes life-threatening diseases including breakdown of blood vessel. Here, we explored a strategy how endothelial cells could defense against invaded GAS. Vascular endothelial growth factor (VEGF) promotes many diverse biological functions in endothelial cells. We found that supplement of VEGF significantly enhanced GAS clearance in endothelial cells. VEGF inactivated mTOR activity, which resulted in an activation of TFEB, a transcriptional factor crucial for lysosome/autophagy biogenesis. Xenophagy was also partially rescued in VEGF-treated endothelial cells. Furthermore, there is a low VEGF concentration existing in GAS-infected patient sera accompanied with serious disease symptom, such as sepsis also our animal infection model. These suggest endothelial cells are short of VEGF stimulation under GAS infectious condition. We aim to develop this finding toward a future clinical application.
|
| Academic Significance and Societal Importance of the Research Achievements |
GAS bacteria causes life-threatening diseases. Patients are usually companion with body liquid lost and low blood pressure and shock, due to the blood vessel damage. Here, we provide a strategy for clinical therapy that VEGF may be an option for supplement with antibiotic treatment.
|
