RNA sequencing analysis reveals the impact of Schistosoma japonicum worm on host liver fibrosis.

Schistosomiasis, a neglected tropical disease caused by Schistosoma species, remains a significant global health issue. One of its severe complications is liver fibrosis. The role of schistosome worms in liver fibrosis has been largely understudied, with most research focusing on the effects of schistosome eggs. This study investigates the direct impact of Schistosoma japonicum worms on liver fibrosis and explores the potential molecular mechanisms, particularly the role of microRNAs (miRNAs) secreted by the worms. RNA sequencing and small RNA sequencing were employed to investigate the effects of S. japonicum worms on hepatic stellate cells (HSCs) within a Transwell co-culture system. Bioinformatic tools were utilized to predict target genes for identified S. japonicum-derived miRNAs. A mouse model was used, encompassing both bisexual and single-sex male worm infections. Immunohistochemistry and fluorescence in situ hybridization revealed that S. japonicum infection significantly upregulated fibrosis-related proteins in liver tissues, particularly in the periportal regions in the single-sex male infection group. RNA-seq analysis indicated that schistosome worms could influence the gene expression profiles of HSCs, with significant enrichment in collagen organization and fibrosis-related signaling pathways. miRNA profiling identified several Sj-miRNAs, including sja-miR-277, which was shown to inhibit HSC proliferation and activation in vitro. Co-localization of sja-miR-277 with the HSC activation marker α-SMA in liver sections confirmed the involvement of worm-derived miRNAs in HSC activation. Overall, these findings provide novel insights into the role of worm-derived molecules in schistosome-induced liver fibrosis and highlight potential targets for therapeutic intervention.