Fetuin-B Overexpression Promotes Inflammation in Diabetic Retinopathy Through Activating Microglia and the NF-B Signaling Pathway

Purpose: To investigate the expression, source, role, and mechanism of Fetuin-B (FETUB) in diabetic retinopathy (DR).Methods: ELISA and immunofluorescence were used to analyze the concentration of FETUB in plasma, aqueous fluid, and tissue specimens of patients with DR and healthy controls. Immunofluorescence, q-PCR, and western blotting were used to examine the expression of FETUB in DR mice and cells cultured with different concentrations of glucose. BV2 microglia cell line and DR mice were treated using FETUB recombination protein and FETUB shRNA to explore the function of FETUB in DR by q-PCR, western blotting, and immunofluorescence.Results: FETUB concentrations in plasma, aqueous fluid, and tissue specimens were significantly increased in DR patients. The mice in DR group had a higher concentration of FETUB in the retina and liver tissues than those in the control group, and the expression of FETUB was increased in both ARPE19 and BV2 cells under a high-glucose environment. The ratio of p-P65 (Phospho-P65)/P65 and the expression levels of TNF-alpha, VEGF, and ionized calcium binding adaptor molecule (IBA)-1 were increased in BV2 cells cultured with FETUB recombinant protein, while they were decreased in BV2 cells transfected with FETUB shRNA. Immunofluorescence staining showed that there were more IBA-1(+) activated microglia in the retinas of the FETUB recombination protein group than in the retinas of the DR group, and there were fewer IBA-1(+) activated microglia in the retinas of the FETUB shRNA group than in the retinas of the DR group.Conclusions: FETUB sourced from endocrine, autocrine, and paracrine pathways could promote inflammation in DR by activating the NF-kappa B pathway and microglia.