The NF-κB signalling pathway and TM7SF3 contribute to liver fibrosis caused by secreted phospholipase A2 of Clonorchis sinensis

Background The NF-κB signalling pathway has been reported to be related to liver fibrosis, and we investigated whether the NF-κB signalling pathway is involved in liver fibrosis caused by secreted phospholipase A2 of Clonorchis sinensis ( Cs sPLA2). Furthermore, expression of the receptor of Cs sPLA2 on the cell surface of hepatic stellate cells (HSCs) may greatly contribute to liver fibrosis. Methods Cs sPLA2 was administered to BALB/c mice by abdominal injection. The levels of markers of NF-κB signalling pathway activation in mouse liver tissue were measured by quantitative RT-PCR, ELISA and western blot. Additionally, HSCs were incubated with Cs sPLA2, and an NF-κB signalling inhibitor (BAY 11-7082) was applied to test whether the NF-κB signalling pathway plays a role in the effect of Cs sPLA2. Then, the interaction between Cs sPLA2 and its receptor transmembrane 7 superfamily member 3 (TM7SF3) was confirmed by co-immunoprecipitation (co-IP) and GST pull-down. To determine how TM7SF3 influences the ability of Cs sPLA2 to cause liver fibrosis, a TM7SF3 antibody was used to block TM7SF3. Results The levels of the NF-ΚB signalling pathway activation markers TNF-α, IL-1β and phospho-p65 were increased by Cs sPLA2 in the context of liver fibrosis. In addition, the interaction between TM7SF3 and Cs sPLA2 was confirmed by co-IP and GST pull-down. When TM7SF3 was blocked by an antibody targeting 1–295 amino acids of TM7SF3, activation of HSCs caused by Cs sPLA2 was alleviated. Conclusions The NF-ΚB signalling pathway is involved in the activation of HSCs by Cs sPLA2. TM7SF3, the receptor of Cs sPLA2, plays important roles in liver fibrosis caused by Cs sPLA2. Graphical Abstract