转录因子21调节心脏肌纤维细胞的形成和纤维化
Anne Katrine Z Johansen1, Rajesh K Kasam1, Ronald J Vagnozzi1,2
1Division of Molecular Cardiovascular Biology (A.K.Z.J., R.K.K., R.J.V., S.-C.J.L., S.L.K.B., Y.K., K.M.G., K.W., M.A.S., T.A.B., J.D.M.), Department of Pediatrics, University of Cincinnati and Cincinnati Children's Hospital Medical Center, OH.
Circulation research
|December 4, 2024
概括
转录因子21 (TCF21) 不能维持成人心脏纤维细胞的身份,但在抑制其下调时可以防止纤维化. 预防TCF21损失可以减少肌纤维细胞的形成和受伤后的心脏纤维化.
科学领域:
- 心血管生物学 心血管生物学
- 细胞和分子医学 细胞和分子医学
- 纤维化研究 纤维化研究
背景情况:
- TCF21 (转录因子21) 是一个bHLH蛋白,对胚胎心脏纤维细胞 (CF) 发育至关重要.
- 在成人心脏中,TCF21在受伤期间下调,这表明它在调节纤维细胞分化和纤维化中的作用.
研究的目的:
- 研究TCF21在成人心脏纤维细胞分化和心脏纤维化中的作用.
- 确定TCF21功能增益和功能丧失对心脏损伤反应的影响.
主要方法:
- 使用泰莫西芬诱导的CRE小鼠模型在成人CF中进行TCF21删除或强制表达.
- 进行了组织学,心声学和转录学分析.
- 通过ChIP-seq.确定了基因组TCF21占用率.
- 用心肌梗塞和AngII/phenylephrine模型用于心脏纤维化.
主要成果:
- 成年CF的TCF21缺失没有影响纤维细胞数量,肌纤维细胞分化或纤维化.
- 强制TCF21表达抑制了肌纤维细胞分化,并减少了心脏纤维化和缩.
- 持续的TCF21表达阻止了纤维化相关基因和ECM组织的诱导.
结论:
- 对于保持成年CF身份,TCF21并不是必不可少的.
- 在受伤期间抑制TCF21下调,可以减少肌纤维细胞的形成,心脏纤维化和急性缩反应.
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