Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis

Molecular targeted agents are pharmacologically used to treat liver fibrosis and have gained increased attention. The present study examined the preventive effect of lenvatinib on experimental sinusoidal capillarization as well in vitro phenotypes hepatic stellate cells. LX-2, a human cell line, was for studies. In vivo induced F344 rats using carbon tetrachloride by intraperitoneal injection 8 weeks, oral administration started two weeks after initial tetrachloride. Lenvatinib restrained proliferation promoted apoptosis LX-2 with suppressed phosphorylation extracellular signal-regulated kinase 1/2 AKT. It also down-regulated COL1A1, ACTA2 TGFB1 expressions inhibiting transforming growth factor-?1/Smad2/3 pathway. Treatment platelet-derived factor-BB-stimulated proliferation, chemotaxis vascular endothelial factor-A production, basic fibroblast factor-induced proliferation. showed that attenuated development reduction activated cells mRNA expression profibrogenic markers. Intrahepatic neovascularization ameliorated reduced Vegf1, Vegf2 Vegfa lenvatinib-treated rats. Collectively, these results suggest potential use novel therapeutic strategy fibrosis.