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

Lou,Dayong; Han,Jibo; Zhou,Liqin; Ma,Huanjie; Xv,Jianjiang; Shou,Junwei; Xu,Zhixiu; Jiang,Liqin; Qian,Yuanyuan

doi:10.3892/etm.2018.6586

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

Authors:
- Dayong Lou
- Jibo Han
- Liqin Zhou
- Huanjie Ma
- Jianjiang Xv
- Junwei Shou
- Zhixiu Xu
- Liqin Jiang
- Yuanyuan Qian
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Affiliations: Medication Department, Zhuji People's Hospital of Zhejiang Province, Zhuji, Shaoxing, Zhejiang 311800, P.R. China, Department of Cardiology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
Published online on: August 7, 2018 https://doi.org/10.3892/etm.2018.6586
Pages: 2909-2916
Copyright: © Lou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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