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

Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis.
J Cell Mol Med. 2021 Feb 20;:
Authors: Ogawa H, Kaji K, Nishimura N, Takagi H, Ishida K, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Yoshiji H
Abstract
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 liver fibrosis and sinusoidal capillarization as well as the in vitro phenotypes of hepatic stellate cells. LX-2, a human stellate cell line, was used for in vitro studies. In vivo liver fibrosis was induced in F344 rats using carbon tetrachloride by intraperitoneal injection for 8 weeks, and oral administration of lenvatinib was started two weeks after initial injection of carbon tetrachloride. Lenvatinib restrained proliferation and promoted apoptosis of LX-2 with suppressed phosphorylation of extracellular signal-regulated kinase 1/2 and AKT. It also down-regulated COL1A1, ACTA2 and TGFB1 expressions by inhibiting the transforming growth factor-β1/Smad2/3 pathway. Treatment with lenvatinib also suppressed platelet-derived growth factor-BB-stimulated proliferation, chemotaxis and vascular endothelial growth factor-A production, as well as basic fibroblast growth factor-induced LX-2 proliferation. In vivo study showed that lenvatinib att...

Source: J Cell Mol Med - February 20, 2021 Category: Molecular Biology Authors: Ogawa H, Kaji K, Nishimura N, Takagi H, Ishida K, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Yoshiji H Tags: J Cell Mol Med Source Type: research