Hepatic fibrosis is a pathological process in which extracellular matrix excessively aggregates in an injured liver. Research on hepatic fibrosis is expanding, however, much information in this process is still unclear. Here, we examined the gene expression changes within the process of liver fibrosis, providing the first evidence that secreted S100A6 is a critical contributor. We discovered that expression of the S100 family is highly correlated with CCl4-induced liver fibrosis and post self-recovery in mice. Recombinant human S100A6 (rhS100A6) introduced to CCl4-induced mice was found to enhance liver fibrosis through the promotion of activated hepatic stellate cell (HSC) proliferation. More importantly, we showed that rhS100A6 can induce cell cycle transition from S to G2 stage and significantly elevate the level of ERK phosphorylation in the MARK pathway. In contrast to rhS100A6, recombinant human and soluble receptor for advanced glycation end products (sRAGE), a natural antagonist of the S100/RAGE pathway, was found to have a preventative effect on liver fibrosis in CCl4-induced mice. In conclusion, our study supports that S100A6 could be a novel therapeutic in liver fibrosis and its receptor antagonist, sRAGE, proofed to be effective for the treatment of liver fibrosis.
Keywords: Hepatic stellate cells (HSC); Liver fibrosis; S100A6; Soluble receptor for advanced glycation end products (sRAGE).
Copyright © 2018. Published by Elsevier B.V.