GSDMD-mediated Pyroptosis of Synovial Vascular Endothelial Cells Promotes Joint Destruction in Rheumatoid Arthritis
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20240907.008
- VernacularTitle:焦孔素D介导的滑膜血管内皮细胞焦亡促进类风湿关节炎关节破坏
- Author:
Tao WU
1
;
Xuepei ZHANG
;
Ye LU
;
Yaowei ZOU
;
Zhiming OUYANG
;
Jianda MA
;
Lie DAI
Author Information
1. 中山大学孙逸仙纪念医院风湿免疫科,广东 广州,510120
- Keywords:
pyroptosis;
rheumatoid arthritis;
gasdermin D;
vascular endothelial cells;
joint destruction
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2024;45(5):709-718
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To explore the occurrence of gasdermin D(GSDMD)-mediated pyroptosis and its effect on cell proliferation,migration and tubular formation abilities of synovial vascular endothelial cells(VEC)in rheumatoid arthritis(RA).[Methods]Synovium tissues from knee joints of 22 RA patients and 18 orthopaedic arthropathies(Orth.A)patients were collected.The level of activated GSDMD-NT segment in synovium was detected by Western blot.The clinical characteristics of RA patients were compared between high and low synovial GSDMD-NT groups.The cell localization of GSDMD in RA synovium was detected by immunofluorescence staining.RA synovial fluid was added to the culture of human umbilical vein endothelial cells(HUVEC)in vitro,and the level of apoptosis and expression of pyroptosis pathway proteins were detected.The effects of GSDMD on apoptosis,proliferation,migration and tubule formation of HUVEC cells were analyzed.[Results]GSDMD expression in RA synovium was significantly higher than that in Orth.A,and more severe joint destruction and higher microvascular count score were found in RA patients with high GSDMD-NT expression.Synovial VEC had positive expression of GSDMD.Stimulation with RA synovial fluid could induce GSDMD-mediated pyroptosis in HUVEC,increased the secretion of vascular endothelial growth factor(VEGF)and their abilities of proliferation,migration and tubule formation.Knockdown of GSDMD could reverse the above effects.[Conclusion]GSDMD-mediated pyroptosis of partial synovial VEC aggravates RA joint destruction through VEGF secretion that promotes proliferation,migration and angiogenesis of the remaining VEC,which may be a new target to block neovascularization and inhibit joint destruction in RA.
