| 研究実績の概要 |
The goal of this project is to clarify the mechanism of VEGF-TFEB mediated antimicrobial effects for endothelial cell defense against GAS infection. In 2019, I had completed specific aim 2 and specific aim 3.
last year, the results in the aim 1, I had found VEGF provide suppression effects for endothelial cell to again GAS. For specific aim 2, I demonstrated VEGF-mediated antimicrobial activity through TFEB activation. VEGF induces Ca2+release and partially affects mTORC1 activity. Ca2+ level was confirmed by Fluo8 stain. VEGF mediated TFEB nuclear trans-localization. Bacterial number was affected by TFEB overexpression or siRNA knockdown confirmed TFEB is required for GAS clearance. I also clarified that VEGF-mediated TFEB activation rescue xenophagy in endothelial cells. Since TFEB activation also increase autophagy, I detected autophagy related gene FIP200 recruitment on GAS-containing vesicles and found the efficiency was enhanced by VEGF. Most importantly, I found VEGF mediated a successful autophagosome, isolation membrane (IM), target on GAS under electron microscope observation. I concluded that VEGF-mediated TFEB activation could even more rescue xenophagy against GAS in endothelial cells.
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