Host angiogenic reprogramming by Echinococcus multilocularis protoscoleces protein via PDGFR/PI3K/AKT cascade

Area of Science:

• Parasitology
• Molecular Biology
• Pathology

Background:

• Alveolar echinococcosis (AE) is a serious zoonotic disease caused by Echinococcus multilocularis (E. multilocularis).
• AE presents as liver tumor-like growths and can metastasize, sharing similarities with cancer, including pathological angiogenesis.
• The precise mechanisms of angiogenesis in AE remain largely unknown.

Purpose of the Study:

• To investigate the role of angiogenesis in E. multilocularis infection.
• To elucidate the molecular pathways driving pathological angiogenesis in AE.
• To identify potential anti-angiogenic therapeutic targets for AE.

Main Methods:

• Established a mouse model of E. multilocularis infection.
• Analyzed angiogenesis-related gene expression.
• Utilized in vitro assays with specific pathway inhibitors (AG1296, LY294002, MK2206, Y15) to probe the EmP-induced angiogenesis mechanism.

Main Results:

• Significantly upregulated angiogenesis-related genes were observed in infected mice.
• Pathological angiogenesis around lesions increased markedly 10-12 weeks post-infection.
• E. multilocularis protoscoleces protein (EmP) was confirmed to induce angiogenesis via the PDGFR/PI3K/AKT/FAK signaling pathway.

Conclusions:

• E. multilocularis infection triggers pathological angiogenesis in the liver through the PDGFR/PI3K/AKT/FAK pathway.
• These findings offer novel insights into AE pathogenesis.
• This research may pave the way for new anti-angiogenic treatments against E. multilocularis infection.