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多组学和实验验证确定甲基化相关的基因和METTL16作为糖尿病足病原发生的关键调节者
Yilan Tong1, Sicheng Li1, Lei Shen2
1Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Scientific reports
|November 27, 2025
概括
与甲基化相关的基因 (MRG) 是糖尿病足 (DFU) 的关键. 作为一个诊断生物标志物和治疗目标,METTL16显示出改善DFU愈合的希望.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 糖尿病学 糖尿病学
背景情况:
- 糖尿病足 (DFU) 由于受损的伤口愈合和慢性炎症,存在重大挑战.
- N6-甲基氨酸 (m6A) 修饰因其在调节基因表达和与伤口愈合相关的细胞功能中的作用而越来越受认可.
研究的目的:
- 系统地调查甲基化相关基因 (MRG) 在糖尿病足 (DFU) 病变发生过程中的作用.
- 通过综合性多学科分析和实验验证,识别潜在的诊断生物标志物和DFU的治疗点.
主要方法:
- 对大量RNA-seq,微阵列和单细胞RNA测序 (scRNA-seq) 数据集的分析,以识别差异表达MRG (DE-MRG).
- 机器学习算法的应用 (LASSO,GBM,SVM-RFE,随机森林) 用于生物标志物选.
- 在高葡萄糖处理的人体皮肤纤维细胞 (HSFs) 中进行免疫透,通路丰富和功能测试.
主要成果:
- 在DFU组织中发现了13种DE-MRG,其中METTL16,NSUN3和IGF2BP2被突出显示为潜在的诊断生物标志物.
- 免疫分析表明M1巨细胞的丰富和IL-17/MAPK通路的失调.
- METTL16在高血糖菌中发挥了保护作用,增强了迁移,原合成,并在高血糖条件下降低了氧化应激.
结论:
- 与甲基化相关的基因是DFU病变发生的关键调节者.
- METTL16被确定为糖尿病足的有前途的诊断生物标志物和治疗标.
- 这项研究为DFU分子机制提供了新的见解,为诊断和治疗提出了新的途径.
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