Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, People's Republic of China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Sci Rep. 2017 Jul 12;7(1):5212. doi: 10.1038/s41598-017-05602-8.
Schistosomiasis caused by schsitosomes is a serious global public health concern. The tegument that surrounds the worm is critical to the schistosomes survival. The tegument apical membrane undergoes a continuous process of rupture and repair owing to membranous vacuoles fusing with the plasma membrane. Vesicle-associated membrane protein 2 (VAMP2), a member of soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNAREs) is required for membrane fusion. Here, we used RNA interference (RNAi) to knock down the expression of VAMP2 of Schistosoma japonicum (SjVAMP2), and both real-time PCR and western blot analysis confirmed the suppression of this molecule, as well as the suppression of the transcript levels of schistosome glucose transporters (SGTP1 and SGTP4), and insulin receptors (SjIR1 and SjIR2). SjVAMP2-suppressed worms exhibited a lower viability, and phenotypic alterations were also observed in the tegument. Moreover, the glucose consumption of SjVAMP2-suppressed worms decreased significantly in 4 and 6 days, respectively, as well as a significant reduction in egg production. We also observed a significant reduction in worm burden and hepatic eggs burden in two independent RNAi experiment in vivo, and minor pathological changes in mice treated with SjVAMP2 specific small interfering (si)RNA. These findings reveal that SjVAMP2 may play important roles in the maintenance of tegument, glucose uptake, worm development and egg production in schistosomes.
由血吸虫引起的血吸虫病是一个严重的全球公共卫生问题。蠕虫周围的表皮对于血吸虫的生存至关重要。由于膜泡与质膜融合，表皮顶膜经历连续的破裂和修复过程。囊泡相关膜蛋白 2（VAMP2）是可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体（SNAREs）的成员，是膜融合所必需的。在这里，我们使用 RNA 干扰（RNAi）敲低日本血吸虫（SjVAMP2）的 VAMP2 表达，实时 PCR 和 Western blot 分析证实了该分子的抑制，以及血吸虫葡萄糖转运蛋白（SGTP1 和 SGTP4）和胰岛素受体（SjIR1 和 SjIR2）的转录水平的抑制。SjVAMP2 抑制的蠕虫表现出较低的活力，表皮也出现了表型改变。此外，SjVAMP2 抑制的蠕虫在第 4 天和第 6 天的葡萄糖消耗分别显著下降，产卵量也显著减少。我们还在体内进行了两次独立的 RNAi 实验，观察到蠕虫负荷和肝卵负荷显著减少，用 SjVAMP2 特异性小干扰（si）RNA 处理的小鼠也观察到轻微的病理变化。这些发现表明 SjVAMP2 可能在维持血吸虫表皮、葡萄糖摄取、蠕虫发育和产卵中发挥重要作用。
