Fibroblast growth factor receptor 1 antagonism attenuates lipopolysaccharide-induced activation of hepatic stellate cells via suppressing inflammation

Activated hepatic stellate cells (HSCs) serve key roles in hepatic fibrosis by producing excessive extracellular matrix (ECM) components. Lipopolysaccharide (LPS) has been found to be associated with hepatic fibrogenesis through direct interactions with HSCs. Recently, the fibroblast growth factor receptor 1 (FGFR1) signalling system was identified as a key player in the process of liver fibrosis. In the present study it was evaluated whether FGFR1 mediated LPS-induced HSCs activation. In cultured cells, FGFR1 was inhibited by either siRNA silencing or by a small-molecule inhibitor in LPS-stimulated HSCs. The blockade of FGFR1 decreased LPS-induced nuclear factor-κB (NF-κB) activation, inflammatory cytokine release, fibrosis, and cell proliferation in HSCs. It was further indicated that LPS triggered FGFR1 phosphorylation via TLR4/c-Src. These findings confirmed the detrimental effect of FGFR1 activation in the pathogenesis of LPS-related HSC activation and revealed that FGFR1 may be an ideal therapeutic target for LPS-induced liver fibrosis.