Targeted Inhibition of Growth Differentiation Factor 3 Attenuates Endothelial Cell Inflammatory Response and Suppresses Choroidal Neovascularization
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20250512.001
- VernacularTitle:靶向抑制生长分化因子3减轻内皮细胞炎症反应并抑制脉络膜新生血管
- Author:
Rongsui TANG
1
;
Yi TIAN
1
;
Zhen XIONG
1
;
Xuri LI
1
Author Information
1. 中山大学中山眼科中心眼病防治全国重点实验室,广东 广州 510623
- Publication Type:Journal Article
- Keywords:
age-related macular degeneration;
choroidal neovascularization;
growth differentiation factor 3;
vascular endothelial cell;
inflammation
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2025;46(4):607-618
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To investigate the effects of targeted inhibition of growth differentiation factor 3(GDF3)on choroidal neovascularization(CNV)and endothelial inflammatory response.[Methods]A laser-induced CNV mouse model was established,and differentially expressed genes were screened by RNA sequencing(RNA-seq).GDF3 expression was validated by real-time fluorescence quantitative PCR(RT-qPCR)and Western blot.GDF3 in endothelial cells was antagonized by siRNA and neutralizing antibodies.Functional assays including CCK8 assay,scratch assay,and tube formation assay were performed to assess endothelial cell proliferation,migration,and angiogenic capacity.The expression changes of inflammatory/adhesion molecules were measured,and immune cell adhesion and transendothelial migration were analyzed.In the CNV model,shRNA was intravitreally injected to suppress GDF3 expression,with CNV lesions and immune cell infiltration quantified by immunofluorescence staining.[Results]GDF3 expression was significantly upregulated in CNV tissues(P＜0.001).In vitro GDF3 intervention markedly suppressed endothelial cell proliferation(P＜0.001),migration(P＜0.001),and angiogenesis(P＜0.01),downregulated the expression of inflammatory/adhesion molecules(P＜0.001),and significantly reduced immune cell adhesion(P＜0.001)and transendothelial migration(P＜0.001).In vivo experiments confirmed that targeted inhibition of GDF3 significantly attenuated CNV formation(P＜0.001)and decreased immune cell infiltration(P＜0.001).[Conclusion]Targeted inhibition of GDF3 concurrently attenuates endothelial inflammatory response and pathological angiogenesis,potentially through modulating the inflammatory microenvironment.These findings provide novel insights for the treatment of wet age-related macular degeneration(wAMD).
