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

Abstract EN

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 induction.

During tTG inhibition, TGF-β1 level decreased in sera and liver of infected mice.

TGF-β1 showed positive staining in liver containing Sj adult worms and eggs.

TGF-β1 was also detected in Sj adult worm sections, soluble egg antigen and Sj adult worm antigen, and adult worms’ culture medium.

The TGF-β1 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-β1 transcript in Sj eggs was higher than in adult worms.

In Sj-infected liver, transcriptional level of TGF-β1 from Sj, but not mouse liver, correlated with liver fibrosis extent.

This study provides evidence that tTG regulates TGF-β1 and illustrates the importance of targeting tTG in treating Sj infection-induced fibrosis.