Proteomic analysis of the effects of Nur77 on lipopolysaccharide-induced microglial activation

Microglia are critical components of the immune response in the central nervous system. Our study aims to explore potential role of Nur77 in lipopolysaccharide (LPS)-induced microglial activation. Primary wild-type and Nur77^-/- microglia were stimulated with LPS and protein extracts were detected via mass spectrometry. Q-PCR and western blotting were performed to validate candidate proteins. A total of 2004 proteins were identified, with 749 and 677 significantly differentially expressed proteins in wild-type and Nur77^-/- microglia in resting and activated states, respectively. Signaling pathway analysis showed that significantly differentially expressed proteins in LPS-treated Nur77^-/- microglia were present in important signaling pathways of microglial activation, including the Toll-like receptor signaling pathway, the MAPK signaling pathway, FcγR-mediated phagocytosis, and chemokine signaling pathways. Furthermore, we found that Nur77 could be the upstream protein of the vav1 and ERK1/2 signaling pathway. This study provided new insights into the understanding the mechanisms of the effects of Nur77 on LPS-activated microglia.