VEGF (vascular endothelial growth factor) provides antimicrobial effects via autophagy and lysosomal empowerment in endothelial cells
VEGF (vascular endothelial growth factor) provides antimicrobial effects via autophagy and lysosomal empowerment in endothelial cells
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VEGF（血管内皮生长因子）通过内皮细胞自噬和溶酶体赋权提供抗菌作用
DOI：
10.1080/27694127.2022.2137755
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Noda Takeshi
中科院分区：
文献类型：
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作者：
Lu Shiou-Ling;Noda Takeshi
异种吞噬是一种细胞内防御入侵病原体的机制。在上皮细胞中，化脓性链球菌(无链球菌，GAS)通过这一过程被有效地清除。然而，我们先前报道，异种吞噬的效果因细胞类型不同而不同；内皮细胞异种吞噬的内在缺陷未能抑制气体生长。考虑到与上皮细胞相比，内皮细胞中异种吞噬的基础水平较低，可能需要额外的刺激来增强这种活性。最近，我们报道了血管内皮生长因子是促进内皮细胞异种吞噬和溶酶体活性的关键因素。这些过程进一步导致对入侵气体的有效杀灭。激活转录因子EB(转录因子EB)的信号通路中的cAMP-IP3-Ca~(2+)轴支持血管内皮生长因子信号的转导。此外，在小鼠模型和人类患者中，观察到脓毒症的严重程度与血清中低水平的血管内皮生长因子浓度有关。应用血管内皮生长因子可降低气体脓毒症模型的死亡率。基于这些发现，我们认为，血管内皮生长因子通过提供强大的血管屏障来增强内皮细胞内的防御系统，以防止细菌传播。
Xenophagy is an intracellular defense mechanism against invading pathogens.Streptococcus pyogenes(group AStreptococcus, GAS) is efficiently eliminated by this process in epithelial cells. However, we previously reported that the efficacy of xenophagy differs among cell types; intrinsic deficits in endothelial cell xenophagy failed to suppress GAS growth. Considering that the basal level of xenophagy is lower in endothelial cells as compared to epithelial cells, additional stimulation may be required to enhance this activity. Recently, we reported that VEGF (vascular endothelial growth factor) is the key factor facilitating xenophagy and lysosomal activity in endothelial cells. These processes further lead to the efficient killing of invading GAS. The cAMP-IP3-Ca2+axis of the signaling pathway that activates TFEB (transcription factor EB) supports the transduction of the signal from VEGF. In addition, the severity of sepsis was observed to correlate with low VEGF concentrations in serum, both in a mouse model and in human patients. VEGF administration reduces mortality in a GAS sepsis model. Based on these findings, we propose that VEGF boosts the intracellular defense system of the endothelium by providing a strong blood vessel barrier to prevent bacterial dissemination.