Fetuin-B Overexpression Promotes Inflammation in Diabetic Retinopathy Through Activating Microglia and the NF-κB
Wenyi Zhang1, Jing Yao1, Chen Chen2
1Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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-α, 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-κB pathway and microglia.
Insights
Fetuin-B (FETUB) is elevated in diabetic retinopathy (DR) and promotes inflammation by activating microglia via the NF-κB pathway. Reducing FETUB may offer a therapeutic strategy for DR.
Area of Science:
- Ophthalmology
- Endocrinology
- Immunology
Background:
- Diabetic retinopathy (DR) is a microvascular complication of diabetes, leading to vision loss.
- Understanding the molecular mechanisms underlying DR pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the expression, source, role, and mechanism of Fetuin-B (FETUB) in diabetic retinopathy (DR).
Main Methods:
- Analyzed FETUB concentrations in patient samples (plasma, aqueous fluid, tissues) and DR mouse models using ELISA and immunofluorescence.
- Examined FETUB expression in high-glucose-cultured cells and DR mice via immunofluorescence, q-PCR, and western blotting.
- Investigated FETUB's function in DR using recombinant protein and shRNA in BV2 microglia and DR mice.
Main Results:
- FETUB levels were significantly increased in DR patients and in the retinas and livers of DR mice.
- High glucose upregulated FETUB expression in ARPE19 and BV2 cells.
- FETUB promoted inflammation in BV2 cells by activating the NF-κB pathway and increasing TNF-α, VEGF, and IBA-1 expression, while FETUB inhibition reversed these effects.
Conclusions:
- Fetuin-B (FETUB) is upregulated in diabetic retinopathy (DR).
- FETUB, from various sources, promotes DR-associated inflammation by activating the NF-κB pathway and microglia.
- Targeting FETUB may be a potential therapeutic approach for managing DR.
