The potential protective effect of niclosamide in a model of experimentally-induced liver fibrosis in rats

Abstract

Cholestasis is considered as one of the most significant stimulus for fibrotic liver. It is characterized by severe increase in liver and serum bile acid levels that leads to liver toxicity followed by fibrosis and cirrhosis. Activation of cholangiocytes proliferation is thought to help initiate and progress cholestatic liver fibrosis. HPCs are the source of proliferating cholangiocytes and Notch signaling promotes the differentiation of HPCs to cholangiocytes. The proliferating cholangiocytes then secrete profibrotic factors which induces activation and proliferation of HSCs to produce collagen and α-SMA that induces ECM deposition and fibrotic progression. Additionally, there are other signaling pathways involved in cholangiocytes proliferation including non-canonical Wnt signaling pathway that functions independently from β-catenin. Till now, no therapy could effectively inhibit abnormal activation of cholangiocytes.