Blockade of IGFBPrP 1 attenuates canine hepatic fibrosis induced by thioacetamide via inhibition of hepatic stellate cell activation

Here we aimed to investigate the anti-fibrotic effect of the antibody against insulin-like growth factor binding protein-related protein 1 in a hepatic fibrosis canine model and explored the underlying mechanism. Advanced liver fibrosis was induced in beagles by thioacetamide administration for 12 weeks. From the 5th week, the animals received the antibody injections via the portal vein once a week. Liver biopsies were performed at weeks 0, 3, 6, 9, and 12. The pathological changes and fibrosis scores were examined. The dynamic changes in the expression of insulin-like growth factor binding protein-related protein 1, α-SMA, phosphorylation of the NF-κB subunit RelA at serine 536, and transforming growth factor β 1 during this process were studied using immunohistochemical methods. Hepatic insulin-like growth factor binding protein-related protein 1 expression significantly increased in the process of liver fibrosis from the 6th week and then sharply decreased from the 9th week due to blockade of insulin-like growth factor binding protein-related protein 1. In addition, the thioacetamide-induced liver fibrosis in the antibody-treated group was markedly attenuated as compared to that in the control group. Furthermore, the elevations in α-SMA, phosphorylation of the NF-κB subunit RelA at serine 536, and transforming growth factor β 1 levels in liver tissues were inhibited. Blockade of insulin-like growth factor binding protein-related protein 1 could ameliorate hepatic fibrosis in the canine model by inhibiting hepatic stellate cell activation and downregulating transforming growth factor β 1 via a mechanism involving the NF-κB pathway.