Abstract: Objective    To explore the effect of hepatocyte growth factor (HGF) on microglia-mediated neuroinflammation and its regulatory mechanism, and to provide experimental basis and theoretical reference for the determination of possible treatment targets.   Methods    The mouse immortalized cell line-BV2 cells, which retain multiple morphological and functional characteristics of microglia, were divided into a control group and a HGF group. The effects of HGF on the activity of NF-κB signaling pathway and subsequent expression of neuroinflammatory factors were determined by tyrosine phosphorylated proteomic analysis, cell survival assay, quantitative real time polymerase chain reaction (qRT-PCR) and western blot (WB).   Results Tyrosine phosphorylated proteomic analysis showed that after addition of HGF, NF-κB signaling was one of the most enriched pathways in BV2 cells. At 1 hour after the addition of HGF with different concentrations, the proliferation activity of BV2 cells was decreased. At both 6 hours and 12 hours after the supplementation of HGF with various concentrations, the proliferation activity of BV2 cells increased at early stage, while decreased at late stage. qRT-PCR found that HGF could upregulate the transcription level of inflammatory factors derived from BV2 cells (iNOS, TNF-α, IL-1β). WB also showed that HGF could promote protein translation of associated inflammatory factors (TNF-α, NF-κB p65).    Conclusions    This study confirms the role of HGF in promoting neuroinflammation by activating the NF-κB signaling pathway in BV2 cells and its mechanism. It provides important clues to further explore the regulatory strategies on neuroinflammation to develop more effective treatment in the clinic.

Key words: Hepatocyte growth factor; ,  , Microglia; ,  , Neuroinflammation; ,  , NF-κB signaling pathway, Factor