The effects of extracellular vesicles derived from Echinococcus granulosus hydatid cyst fluid on the insulin related genes in liver cell line model.

Cystic echinococcosis, caused by the larval stage of Echinococcus granulosus, predominantly affects the liver. Components of hydatid cyst fluid (HCF), including extracellular vesicles (EVs), have been suggested to participate in host-parasite communication. The present study investigated whether HCF and EVs derived from it can influence insulin-related genes in hepatocyte cells. EVs were isolated from the HCF obtained from the liver of an infected sheep using differential centrifugation and were characterized by western blotting, scanning electron microscopy (SEM), dynamic light scattering (DLS), and zeta potential analysis. HepG2 cells were treated with EVs and HCF for 24 and 48 hours. The expression of insulin-related genes, including INSR, AKT, IDE, and INSIG2, was then evaluated by quantitative real-time PCR. EV significantly up-regulated AKT (1.98 ± 0.17, p < 0.0001), INSR (2.09 ± 0.34, P = 0.0008), IDE (1.40 ± 0.17, P = 0.0031), and INSIG2 (1.67 ± 0.17, P = 0.0005) at 24 h; however, at 48 h, AKT (-2.68 ± 0.4), INSR (-3.75 ± 0.4), and IDE (-3.6 ± 0.93) were significantly down-regulated (all P < 0.0001), while INSIG2 remained up-regulated (3.81 ± 0.85, P = 0.0006). In contrast, HCF exposure predominantly caused gene down-regulation, with significant decreases in AKT (-1.41 ± 0.4), INSR (-1.9 ± 0.72), and IDE (-1.6 ± 0.34) at 24 h (all P ≤ 0.0002) and a more pronounced downregulation of all genes at 48 h, including AKT (-6.67 ± 1.56), INSR (-5.89 ± 0.76), IDE (-6.8 ± 1.2), and INSIG2 (-1.16 ± 0.06) (all P < 0.0001). Our findings showed that exposure to EVs was associated with reduced expression of INSR and AKT and increased expression of IDE and INSIG2. This metabolic reprogramming appears to be a coordinated strategy to divert host energetic resources to favor parasite survival.