Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration

被引:3
|
作者
Luo, Jiaying [1 ]
Jin, Guoxin [2 ]
Cui, Shaoqian [2 ]
Wang, Huan [2 ]
Liu, Qi [2 ,3 ]
机构
[1] Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang, Peoples R China
[2] China Med Univ, Dept Orthoped, Shengjing Hosp, Shenyang, Peoples R China
[3] China Med Univ, Dept Orthoped, Shengjing Hosp, 36 Sanhao St, Shenyang 110000, Liaoning, Peoples R China
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2024年 / 602卷 / 07期
关键词
FCGR2A; intervertebral disc degeneration; macrophage polarization; NF-kappa B; nucleus pulposus cells; phosphorylation; SOCS3; STAT family; STAT3; ACTIVATION; PROMOTE; CANCER; CELLS;
D O I
10.1113/JP285871
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co-expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein-protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages. Functional validation through in vitro and in vivo experiments demonstrates the pivotal role of FCGR2A in macrophage polarization and IDD progression. Mechanistically, FCGR2A knockdown suppresses M1 macrophage polarization and NF-kappa B phosphorylation while enhancing M2 polarization and STAT3 activation, leading to ameliorated IDD in animal models. This study sheds light on the regulatory function of FCGR2A in macrophage polarization, offering novel insights for IDD intervention strategies.
引用
收藏
页码:1341 / 1369
页数:29
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