Wnt4, the first member of the Wnt family identified in Schistosoma japonicum, regulates worm development by the canonical pathway

Wnt4, the first member of the Wnt family identified in Schistosoma japonicum, regulates worm development by the canonical pathway
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Wnt4 是日本血吸虫中发现的 Wnt 家族的第一个成员,通过经典途径调节蠕虫发育

DOI:
10.1007/s00436-010-1933-8
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发表时间:
2010-09-01
影响因子:
2
通讯作者:
Lin, Jiao-Jiao
Lin, Jiao-Jiao
中科院分区:
医学3区
文献类型:
--
作者:
Li, Hong-Fei;Wang, Xiao-Bo;Lin, Jiao-Jiao

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Wnt信号通路是一种进化保守的信号转导通路,在动物发育过程中广泛使用。我们的目标是,通过增加我们对Wnt信号通路的理解,发现血吸虫中存在的关键基因或蛋白,可以开发成候选疫苗或药物靶点。因此,我们从日本血吸虫中分离到了Wnt4基因。Wnt4编码一种含有558个氨基酸的蛋白质,其中包含Wnt基因家族的保守功能域。我们通过RNA干扰抑制10天血吸虫Wnt4 mRNA的表达。定量PCR分析显示,Wnt4的转录本水平降低了73%。参与Wnt典型通路的GSK-3 β和β -catenin mRNA水平分别下降45%和39%。参与Wnt非规范通路的PLC、CaMKII、DVL、JNK均无明显降低。这些结果表明,日本血吸虫Wnt4信号蛋白通过典型途径调控下游基因。Wnt4是在日本血吸虫中发现的首个Wnt家族成员。对Wnt信号转导途径的进一步了解将使我们能够进一步阐明血吸虫发育的分子机制。
The Wnt signaling pathway is an evolutionarily conserved signal transduction pathway used extensively during animal development. We aim, by increasing our understanding of the Wnt signaling pathway, to find a key gene or protein present in schistosomes that can be developed into vaccine candidate or drug target. We therefore isolated the Wnt4 gene from Schistosoma japonicum. Wnt4 encodes a putative protein of 558 amino acids which contains the conserved functional domain of the Wnt gene family. We suppressed the expression of Wnt4 mRNA in 10-day schistosomulae by RNA interference. Quantitative PCR analysis showed that Wnt4 displayed a 73% reduction in the transcript level. And GSK-3 beta and beta-catenin, which are involved in Wnt canonical pathway, showed a 45% and 39% reduction in mRNA levels, respectively. PLC, CaMKII, DVL, and JNK, which are involved in Wnt non-canonical pathway, showed no reduction. These results suggest that the Wnt4 signal protein in S. japonicum regulates downstream genes by a canonical pathway. Wnt4 is the first member of the Wnt family to be identified in S. japonicum. An increased understanding of the Wnt signal transduction pathway will allow us to elucidate further the molecular mechanism of development in schistosomes.