Dataset Information

Tissue Transglutaminase-Regulated Transformed Growth Factor-?1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.

ABSTRACT: Transforming growth factor (TGF-?1) is among the strongest factors of liver fibrogenesis, but its association with Schistosoma-caused liver fibrosis is controversial. Tissue transglutaminase (tTG) is the principal enzyme controlling TGF-?1 maturation and contributes to Sj-infected liver fibrosis. Here we aim to explore the consistency between tTG and TGF-?1 and TGF-?1 source and its correlation with liver fibrosis after Sj-infection. TGF-?1 was upregulated at weeks 6 and 8 upon liver fibrosis induction. During tTG inhibition, TGF-?1 level decreased in sera and liver of infected mice. TGF-?1 showed positive staining in liver containing Sj adult worms and eggs. TGF-?1 was also detected in Sj adult worm sections, soluble egg antigen and Sj adult worm antigen, and adult worms' culture medium. The TGF-?1 mature peptide cDNA sequence and its extended sequence were amplified through RT-PCR and RACE-PCR using adult worms as template, and sequence is analyzed and loaded to NCBI GenBank (number GQ338152.1). TGF-?1 transcript in Sj eggs was higher than in adult worms. In Sj-infected liver, transcriptional level of TGF-?1 from Sj, but not mouse liver, correlated with liver fibrosis extent. This study provides evidence that tTG regulates TGF-?1 and illustrates the importance of targeting tTG in treating Sj infection-induced fibrosis.

SUBMITTER: Tang J

PROVIDER: S-EPMC4493306 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Tissue Transglutaminase-Regulated Transformed Growth Factor-β1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.

Tang Juanjuan J Zhu Xunmin X Zhao Jingjing J Fung Mingchiu M Li Yinyan Y Gao Zhiyan Z Yan Suikai S Li Xiaomin X Ji Xiaofang X Su Fang F Li Zi Z

Mediators of inflammation 20150623

Transforming growth factor (TGF-β1) is among the strongest factors of liver fibrogenesis, but its association with Schistosoma-caused liver fibrosis is controversial. Tissue transglutaminase (tTG) is the principal enzyme controlling TGF-β1 maturation and contributes to Sj-infected liver fibrosis. Here we aim to explore the consistency between tTG and TGF-β1 and TGF-β1 source and its correlation with liver fibrosis after Sj-infection. TGF-β1 was upregulated at weeks 6 and 8 upon liver fibrosis in ...[more]

PMID: 26199461

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Project description:BackgroundSchistosomiasis is one of the most common parasitic diseases affecting millions of humans and animals worldwide. Understanding the signal transduction pathways and the molecular basis of reproductive regulation in schistosomes is critically important for developing new strategies for preventing and treating these infections. Syk kinases regulate the proliferation, differentiation, morphogenesis, and survival of various types of cells and have been identified in invertebrates. Tyrosine kinase 4 (TK4), a member of the Syk kinase family, plays a pivotal role in gametogenesis in S. mansoni, affecting the development of the testis and ovaries in this parasite. The role of TK4, however, in the reproduction of S. japonicum is poorly understood.MethodsHere, the complete coding sequence of TK4 gene in S. japonicum (SjTK4) was cloned and characterized. The expression of SjTK4 was analyzed at different life-cycle stages and in various tissues of S. japonicum by qPCR. Piceatannol, a Syk kinase inhibitor, was applied to S. japonicum in vitro. The piceatannol-induced morphological changes of the parasites were observed using confocal laser scanning microscopy and the alterations in important egg-shell synthesis-related genes were examined using qPCR analyses.ResultsSjTK4 mRNA was differentially expressed throughout the life-cycle of S. japonicum. SjTK4 mRNA was highly expressed in the ovary and testis of S. japonicum, with the level of gene expression significantly higher in males than in females. The expression levels of some important egg-shell synthesis related genes were higher in the piceatannol-treated groups than in the vehicle-treated control group and the number of eggs and germ cells also decreased in a concentration-dependent manner. Importantly, large pore-like structures can be found in the testis and ovaries of males and females after treating with piceatannol.ConclusionThe results suggest that SjTK4 may play an important role in regulating gametogenesis of S. japonicum. The findings may help better understand the fundamental biology of S. japonicum. Moreover, the effect of S. japonicum treatment by piceatannol provides us with a new idea that inhibition of SjTK4 signaling pathway can effectively retard the development of the testis and ovaries.

Dataset Information

Tissue Transglutaminase-Regulated Transformed Growth Factor-?1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.

Publications

Tissue Transglutaminase-Regulated Transformed Growth Factor-β1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.

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