心脏纤维细胞衍生的IGFBP6通过合EGR1-MFAP4轴来协调心脏重塑
Shaopeng Cheng1,2, Yilin Wang3,2, Kunsheng Li1,2
1Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
International journal of biological sciences
|November 10, 2025
概括
纤维细胞衍生的胰岛素类生长因子结合蛋白6 (IGFBP6) 通过促进肌纤维细胞分化来驱动心脏纤维化. 向IGFBP6-EGR1-MFAP4通路可以治疗心脏重塑障碍.
科学领域:
- 心血管生物学 心血管生物学
- 纤维化研究 纤维化研究
- 分子医学是分子医学.
背景情况:
- 纤维细胞向肌纤维细胞过渡 (FMT) 驱动心脏纤维化和不良重塑.
- 胰岛素类生长因子结合蛋白6 (IGFBP6) 调节细胞生长,并与纤维化反应有关.
- IGFBP6在心脏纤维细胞激活和重塑中的特定作用尚未完全理解.
研究的目的:
- 研究IGFBP6在纤维细胞介导心脏重塑中的作用.
- 阐明IGFBP6调节肌纤维细胞分化的分子机制.
- 评估针对心脏纤维化中的IGFBP6通路的治疗潜力.
主要方法:
- 在心脏纤维化数据集和患者血清中分析IGFBP6表达.
- 产生的心脏纤维细胞和肌纤维细胞特异性IGFBP6淘汰赛小鼠.
- 评估心脏功能和心肌梗塞 (MI) 或异二醇 (ISO) 挑战后的重塑.
- 利用LC-MS/MS和RNA测序来发现IGFBP6-介导的FMT的分子机制.
主要成果:
- 在纤维性心脏中,IGFBP6的表达上调,与慢性心脏病相关.
- IGFBP6淘汰赛减弱后MI和ISO诱导的心脏重塑和功能障碍.
- 抑制IGFBP6抑制了TGF-β1诱导的FMT.
- IGFBP6与EGR1相互作用,增强EGR1与MFAP4促进体的结合,这是一个亲纤维细胞介质.
结论:
- 来自纤维细胞的IGFBP6是一种通过EGR1-MFAP4轴的心脏纤维化新型调节剂.
- IGFBP6促进肌纤维细胞分化和不良的心脏重塑.
- 准IGFBP6通路为心脏重塑障碍提供了潜在的治疗策略.
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