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山东大学学报 (医学版) ›› 2026, Vol. 64 ›› Issue (5): 50-60.doi: 10.6040/j.issn.1671-7554.0.2025.0945

• 基础医学 • 上一篇    

基质Gla蛋白在脊髓损伤后纤维瘢痕形成中的作用机制

赵相瑞1,阴勇成1,方跃鹏2,杨志杰2,宁斌2   

  1. 1. 山东第二医科大学临床医学院, 山东 潍坊 261053;2.山东第一医科大学附属中心医院脊柱外科, 山东 济南 250013
  • 发布日期:2026-05-13
  • 通讯作者: 宁斌. E-mail:bning@sdfmu.edu.cn
  • 基金资助:
    国家自然科学基金面上项目(82371392);泰山学者特聘专家计划(tstp20231257)

Role and mechanism of matrix Gla protein in fibrotic scar formation after spinal cord injury

ZHAO Xiangrui1, YIN Yongcheng1, FANG Yuepeng2, YANG Zhijie2, NING Bin2   

  1. 1. School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong, China;
    2. Department of Spine Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China
  • Published:2026-05-13

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摘要： 目的 探讨基质Gla蛋白(matrix Gla protein, MGP)在脊髓损伤后纤维瘢痕形成中的作用机制。 方法 选取6只C57BL/6实验小鼠,采用随机分组法分为假手术组(n=3)和脊髓损伤组(n=3)。建立小鼠脊髓损伤模型,于术后第7天,取脊髓损伤组小鼠损伤中心节段和假手术组小鼠解剖学对应节段的脊髓组织,用于转录组学测序分析,筛选出差异表达基因MGP(|log2FC|> 1且Padj< 0.05);采用Western blotting、RT-qPCR和免疫荧光法检测敲低MGP后小鼠胚胎成纤维细胞(mouse embryonic fibroblasts, MEFs)及原代脊髓成纤维细胞纤维化的指标表达,以及转化生长因子-β/Smad(transforming growth factor-β/Smad, TGF-β/SMAD)信号通路的活性变化;采用斜板实验和巴索小鼠运动功能评分(Basso mouse scale, BMS)检测体内成纤维细胞中特异性敲低MGP对小鼠脊髓损伤后运动功能恢复的影响。 结果 转录组测序结果显示,损伤后的脊髓组织中,MGP的表达量显著高于假手术组(P<0.05)。在体外TGF-β 诱导的纤维化进程中,敲低MEFs及原代脊髓成纤维细胞中的MGP基因,使纤维连接蛋白 1、Ⅰ型胶原蛋白、α -平滑肌肌动蛋白的mRNA和蛋白表达水平,以及SMAD家族成员2(SMAD family member 2,SMAD2)和SMAD家族成员3(SMAD family member 3, SMAD3)的磷酸化水平较诱导状态显著降低(P<0.05)。成纤维细胞中特异性敲低MGP,会促进脊髓损伤后小鼠运动功能恢复(P<0.05)。 结论 MGP可能通过靶向TGF-β/SMAD信号通路调控脊髓损伤后纤维瘢痕的形成。

关键词: 脊髓损伤, 基质Gla蛋白, 原代脊髓成纤维细胞, 纤维瘢痕, SMAD家族蛋白

Abstract: Objective To investigate the role and underlying mechanism of the matrix Gla protein(MGP)in fibrous scar formation after spinal cord injury(SCI). Methods Six C57BL/6 mice were randomly assigned to the sham group(n=3)and the spinal cord injury group(n=3). A mouse model of SCI was established. On postoperative day 7, spinal cord tissue was harvested from theepicenter of the lesion of the spinal cord injury group and the anatomically corresponding segments of the sham group for transcriptome sequencing. The differentially expressed gene MGP(|log2FC|>1 and Padj< 0.05)were screened and validated. To investigate the role of MGP, western blotting, RT-qPCR, and immunofluorescence were used to assess the expression of fibrosis markers and the activity of the TGF-β/SMAD signaling pathway in mouse embryonic fibroblasts(MEFs)and primary spinal cord fibroblasts after MGP knockdown. Finally, the inclined plane test and Basso mouse scale(BMS)scores were used to assess the impact of fibroblast-specific MGP knockdown on motor function recovery in mice after SCI. Results The results of transcriptome sequencing showed that the expression of MGP in the spinal cord injury group was higher than in the sham group(P<0.05); During the TGF-β-induced fibrogenesis process, MGP knockdown in MEFs and primary spinal cord fibroblasts significantly reduced the expressions of mRNA and proteins of fibronectin 1, type I collagen, and α-smooth muscle actin, as well as the phosphorylation of SMAD2 and SMAD3, compared to the induced state(P<0.05). The fibroblast-specific suppression of MGP in mice significantly promoted recovery ofmotor function after SCI(P<0.05). Conclusion MGP may modulate fibrous scar formation after SCI by targeting the TGF-β/SMAD signaling pathway.

Key words: Spinal cord injury, Matrix Gla protein, Primary spinal cord fibroblasts, Fibrotic scar, SMAD proteins

中图分类号: 

  • R322.81
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