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.
Current Eye Research
|October 26, 2023
Summary
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.
