AP-1信号调节心脏纤维细胞应激反应
Alexander J Whitehead1,2, Hamza Atcha1,2, James D Hocker3,4
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Journal of cell science
|November 23, 2023
概括
炎症信号激活AP-1通路,使心肌梗塞后心脏纤维化恶化. 特定的遗传变异使GATA5沉默,影响心脏修复中的矩阵生产和细胞信号.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 纤维化研究 纤维化研究
背景情况:
- 矩阵重塑显著影响心肌梗塞后的生存率.
- 人类特异性的非编码调节元素与恶化心肌纤维化有关,但它们的机制尚不清楚.
研究的目的:
- 阐明非编码调节元素影响心肌梗塞后心脏纤维化的机制.
- 研究AP-1信号和GATA5在心脏纤维细胞激活和矩阵生成中的作用.
主要方法:
- 利用诱导多能干细胞衍生的心脏纤维细胞 (iCFs) 来建模心脏病发作后的环境.
- 分析了响应炎症连接体的AP-1转录因子信号通路.
- 研究了9p21位点 (ANRIL) 多态体对GATA5表达和ICF功能的影响.
主要成果:
- 炎症信号激活ICF中的AP-1通路,导致纤维内素基质沉积和免疫细胞粘附.
- 途径抑制减少了iCF矩阵的产生和细胞粘附.
- 在9p21非编码元素中的多态性使iCF中的GATA5沉默,改变了矩阵生成,减少了细胞-细胞信号传输.
结论:
- 已识别的信号轴是心脏病的关键调节器.
- 非编码的调节元件,特别是9p21位点的调节元件,通过调节GATA5表达和纤维细胞行为来影响心脏纤维化.
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