中国医科大学学报2026，Vol.55Issue(3)：265-271,7.DOI:10.12007/j.issn.0258-4646.2026.03.012
miR-224-3p调控JAK/STAT信号通路对LPS诱导的椎间盘退变髓核细胞增殖、凋亡和炎症反应的影响
Effects of miR-224-3p regulating JAK/STAT signaling pathway on proliferation,apoptosis,and inflammatory response of LPS-induced nucleus pulposus cells in intervertebral disc degeneration
摘要
Abstract
Objective To investigate the effects of miR-224-3p regulation of the Janus kinase/signal transducer and activator of tran-scription(JAK/STAT)signaling pathway on the proliferation,apoptosis,and inflammatory response of nucleus pulposus cells in interverte-bral discs.Methods Nucleus pulposus cells were divided into the following groups:Control,Model(intervened with 200 μg/mL lipopoly-saccharide),miR-224-3p negative control(miR-NC),miR-224-3p mimics,miR-224-3p mimics+JAK1 overexpression empty vector(miR-224-3p mimics+pcDNA-NC),and miR-224-3p mimics+JAK1 overexpression plasmid(miR-224-3p mimics+JAK1).miR-224-3p,tumor necrosis factor α(TNF-α),interleukin-6(IL-6),aggrecan,CollagenⅡ,JAK1,and STAT1 mRNA expression levels in cells were determined using real-time quantitative PCR.Cell proliferation was assessed using the Cell Counting Kit-8 assay,and apoptosis was mea-sured using flow cytometry.Inflammatory cytokine levels were determined using enzyme-linked immunosorbent assay kits.JAK1,STAT3,BCL2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2),caspase-3,aggrecan,and CollagenⅡ were analyzed using Western blotting.The targeting relationship between miR-224-3p and JAK1 was verified using a dual-luciferase reporter assay.Results Compared with the Control group,the Model group showed significantly downregulated miR-224-3p expression and upregulated JAK1 and STAT1 expressions in nucleus pulposus cells(P<0.05).miR-224-3p overexpression significantly enhanced cell viability,increased aggrecan,CollagenⅡ,and Bcl-2 protein expression,whereas it reduced the apoptosis rate;TNF-α,IL-6,and IL-8 levels;and the p-JAK1/JAK1 and p-STAT1/STAT1 ratios,as well as caspase-3 and Bax protein expressions(P<0.05).Simultaneous miR-224-3p and JAK1 overexpression reduced cell viability,aggrecan and CollagenⅡ,and Bcl-2 protein expressions,while increasing the apoptosis rate;TNF-α,IL-6,and IL-8 levels,and p-JAK1/JAK1,p-STAT1/STAT1,caspase-3,and Bax protein expressions(P<0.05).Conclusion miR-224-3p expression is signi-ficantly downregulated in nucleus pulposus cells of degenerative intervertebral discs.Notably,miR-224-3p upregulation can enhance the viability of lipopolysaccharide-induced nucleus pulposus cells and inhibit cell apoptosis,inflammatory response,and extracellular matrix degradation by targeting the JAK/STAT signaling pathway.关键词
miR-224-3p/Janus激酶/信号转导和转录激活因子/椎间盘髓核细胞/增殖/凋亡/炎症反应Key words
miR-224-3p/Janus kinase/signal transducer and activator of transcription pathway/intervertebral disc nucleus pulposus cells/proliferation/apoptosis/inflammatory response分类
医药卫生引用本文复制引用
熊和然,赵欣,王松,向超,万骐,程思玲,何生华..miR-224-3p调控JAK/STAT信号通路对LPS诱导的椎间盘退变髓核细胞增殖、凋亡和炎症反应的影响[J].中国医科大学学报,2026,55(3):265-271,7.基金项目
湖北省中医药管理局中医药科研项目(ZY2023M026) （ZY2023M026）
