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Distribution of lethal giant larvae (Lgl) protein in the tegument and negative impact of siRNA-based gene silencing on worm surface structure and egg hatching in Schistosoma japonicum.

Abstract
Lethal giant larvae (Lgl) are an evolutionarily conserved tumor suppressor present in fungi and animals. It plays an essential role in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. Here, we report the presence of Lgl gene in the blood fluke Schistosoma japonicum (SjLgl) (GenBank: KF246684). SjLgl protein was mainly distributed in the unique surface tegument structure by immunofluorescence microscopic staining. Using a simple soaking method, a short interfering RNA (siRNA)-based RNA interference approach knocked down the expression of SjLgl in schistosomula in vitro by up to 89.0%. Moreover, tail vein injection of SjLgl-siRNA into the infected mice reduced SjLgl mRNA levels in vivo by 48.6-85.3%, depending on the duration of treatments. SjLgl-specific siRNA treatment during the infection in mice significantly altered the surface structure of adult worm, featured by the disappearance or significant reduction of sharp spines on the inner all of oral and ventral suckers. The siRNA also reduced the hatching rates in eggs produced by treated mice by up to 85.3%. These observations implied that Lgl plays an important role in the development of tegument in schistosomes, and may be explored as a novel target for developing immuno- and/or small molecule-based therapeutics to control and treat the infections caused by schistosome and other flatworms.
AuthorsYufan Cao, Yanli Shi, Hongbin Qiao, Yunxia Yang, Jinming Liu, Yaojun Shi, Jiaojiao Lin, Guan Zhu, Yamei Jin
JournalParasitology research (Parasitol Res) Vol. 113 Issue 1 Pg. 1-9 (Jan 2014) ISSN: 1432-1955 [Electronic] Germany
PMID24096609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Helminth Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
Topics
  • Animals
  • Helminth Proteins (genetics, metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Ovum (physiology)
  • RNA Interference
  • RNA, Messenger (genetics, metabolism)
  • RNA, Small Interfering (genetics)
  • Rabbits
  • Rats, Wistar
  • Schistosoma japonicum (genetics, metabolism, ultrastructure)
  • Tumor Suppressor Proteins (genetics, metabolism)

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