Host angiogenic reprogramming by <i>Echinococcus multilocularis</i> protoscoleces protein via PDGFR/PI3K/AKT cascade.

Abstract

<h4>Background</h4>Alveolar echinococcosis (AE) is a globally present zoonotic disease caused by <i>Echinococcus multilocularis</i> (<i>E. multilocularis</i>) infection, characterized by the formation of tumor-like growths primarily in the liver, with the potential to spread to other organs. Similar to tumors, <i>E. multilocularis</i> infection is accompanied by pathological angiogenesis, suggesting that the implementation of anti-angiogenic therapeutic strategies may also have promising applications in the treatment of AE. However, the mechanism of angiogenesis in AE remains unclear and has not been fully elucidated.<h4>Results</h4>In this study, we discovered that angiogenesis related genes are significantly up-regulated in the mouse model of <i>E. multilocularis</i> infection and pathological angiogenesis around the lesion was significantly increased at 10-12 weeks after infection compared to the control group. Interventions utilizing a range of inhibitors at the <i>in vitro</i> level, including the PDGFR-β inhibitor AG1296, the PI3K inhibitor LY294002, the AKT inhibitor MK2206, and the FAK inhibitor Y15, demonstrated that <i>E. multilocularis</i> protoscoleces protein (EmP) induces angiogenesis through PDGFR/PI3K/AKT/FAK signaling pathway.<h4>Conclusion</h4>Our findings provide new perspectives on how <i>E. multilocularis</i> infection triggers pathological angiogenesis in the host liver, and may provide a novel anti-angiogenic therapeutic strategy against <i>E. multilocularis</i> infection.