Transcriptomic analysis provides insights into the molecular mechanisms of epigallocatechin-3-gallate to attenuate schistosomiasis hepatic fibrosis in mice

Epigallocatechin-3-gallate (EGCG) was shown to possess anti-inflammatory, anti-infection, and anti-fibrotic effects. Our previous study showed EGCG could attenuate Schistosoma japonicum hepatic fibrosis, however, its underlying molecular mechanisms are still elusive. In this work, RNA-sequencing (RNA-seq) and bioinformatics analyses were used to detect the gene expression alterations in S. japonicum hepatic fibrosis mouse model following EGCG treatment. Our results showed 106 common differentially expressed genes (DEGs) were upregulated in EGCG_LF_vs._Mod_LF (EGCG treatment group relative to S. japonicum infected model group) and downregulated in Mod_LF_vs._Nor_LF (model group relative to normal group), and they are enriched in cytochrome and metabolic genes involving in the metabolism pathways, implying EGCG could improve the S. japonicum egg induced hepatic injury and recover the metabolic functions of the liver. The 410 common DEGs, downregulated in EGCG_LF_vs._Mod_LF and upregulated in Mod_LF_vs._Nor_LF, are associated primarily with inflammation and immunology. Among them, proinflammatory cytokines, chemokines to activate the hepatic stellate cells (HSCs), profibrotic genes, and extracellular matrix (ECM) production and accumulation genes, together with part components of TLR2 and NF-κB signaling pathways, were upregulated in Mod_LF_vs._Nor_LF and downregulated in EGCG_LF_vs._Mod_LF. These results indicate that EGCG treatment could ameliorate S. japonicum egg induced hepatic fibrosis progression via inhibiting the HSCs activation and reducing ECM production and accumulation, which may in part result from suppressing the TLR2 and NF-κB signaling pathways. Our results reveal the molecular mechanisms of EGCG to be used as a potential drug to regress S. japonicum egg induced hepatic fibrosis.