Xu Hao, Yin Luxu, Zou Liang, Zhang Enshui, Cheng Yang, Zhang Wenyue, Liu Yihong, Han Jinxiang, Zhao Yan
Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China; Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
Int Immunopharmacol. 2025 Apr 16;152:114427. doi: 10.1016/j.intimp.2025.114427. Epub 2025 Mar 8.
The mechanisms underlying Rheumatoid Arthritis (RA) remain unclear. Despite having relatively well-defined treatment strategies, current therapeutic approaches only achieve a remission rate of 70 %-80 %, with poor prognosis and no clear diagnostic criteria for early RA. Therefore, there is a need for new therapeutic targets or biomarkers to improve the treatment of RA.
Firstly, we identified the expression characteristics of lysozyme (LYZ) in early RA patients through plasma proteomics and synovial fluid single-cell sequencing analysis. Secondly, we constructed Lyz1 cKO mice to investigate the role of Lyz1 in RA pathogenesis using the Collagen Antibody-Induced Arthritis (CAIA) mouse model. Thirdly, we silenced LYZ to clarify its impact on TNF-α-induced inflammatory cytokine release and other inflammatory phenotypes in MH7A cells. Finally, we explored the cellular pathways involving LYZ in fibroblast-like synoviocytes (FLSs) and changes in RA-related genes through RNA sequencing (RNA-Seq).
LYZ was highly expressed in the plasma and synovial macrophages of early RA patients. The absence of Lyz1 reduced the arthritis course and joint damage in CAIA mice. Silencing LYZ promoted the proliferation and apoptosis of MH7A cells and improved their inflammatory phenotypes, possibly through the regulation of the TNF signaling pathway.
LYZ is highly expressed in the plasma and synovial fluid macrophages of early RA patients and exacerbates RA progression by modulating inflammation-related pathways, demonstrating potential as a biomarker for early RA diagnosis or a therapeutic target.
类风湿关节炎（RA）的发病机制尚不清楚。尽管有相对明确的治疗策略，但目前的治疗方法仅能达到70%-80%的缓解率，预后较差，且早期RA没有明确的诊断标准。因此，需要新的治疗靶点或生物标志物来改善RA的治疗。
首先，通过血浆蛋白质组学和滑液单细胞测序分析确定早期RA患者中溶菌酶（LYZ）的表达特征。其次，构建Lyz1基因敲除小鼠，利用胶原抗体诱导的关节炎（CAIA）小鼠模型研究Lyz1在RA发病机制中的作用。第三，沉默LYZ以阐明其对MH7A细胞中肿瘤坏死因子-α（TNF-α）诱导的炎性细胞因子释放及其他炎性表型的影响。最后，通过RNA测序（RNA-Seq）探索成纤维样滑膜细胞（FLS）中涉及LYZ的细胞途径以及RA相关基因的变化。
LYZ在早期RA患者的血浆和滑膜巨噬细胞中高表达。Lyz1基因缺失可减轻CAIA小鼠的关节炎病程和关节损伤。沉默LYZ可促进MH7A细胞的增殖和凋亡，并改善其炎性表型，可能是通过调节TNF信号通路实现的。
LYZ在早期RA患者的血浆和滑液巨噬细胞中高表达，并通过调节炎症相关途径加剧RA进展，显示出作为早期RA诊断生物标志物或治疗靶点的潜力。
