Transcriptional control of cardiac fibroblast plasticity.
Transcriptional control of cardiac fibroblast plasticity.
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DOI：
10.1016/j.yjmcc.2015.12.016
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发表时间：
2016-02
影响因子：
5
通讯作者：
Small EM
中科院分区：
文献类型：
--
作者：
Lighthouse JK;Small EM
心脏成纤维细胞有助于维持健康心脏的正常结构，并负责瘢痕形成和对病理损伤的愈合反应。各种遗传、生物力学或体液因素刺激成纤维细胞成为收缩性平滑肌样细胞，称为肌成纤维细胞，分泌大量细胞外基质。不幸的是，心脏病中未受抑制的肌成纤维细胞活化导致病理性纤维化，这是心律失常和心力衰竭发展的主要风险因素。更好地理解控制成纤维细胞可塑性和肌成纤维细胞活化的分子机制对于开发新的策略来特异性靶向病理性心脏纤维化而不破坏适应性愈合反应是至关重要的。本文综述了成纤维细胞起源的主要转录介质及其在发育和疾病中的作用。胎儿心外膜基因程序的贡献将讨论的背景下，成纤维细胞起源的发展和以下的损伤，主要集中在Tcf 21和C/EBP。我们还将强调控制成人心脏成纤维细胞可塑性的主要转录调节轴，包括转化生长因子β（TGFβ）/Smad信号传导，Rho/心肌蛋白相关转录因子（MRTF）/血清反应因子（SRF）轴，以及钙调神经磷酸酶/瞬时受体电位通道（TRP）/活化T细胞核因子（NFAT）信号传导。最后，我们将讨论最近的策略，以转移成纤维细胞的转录程序，努力促进心肌细胞再生。这篇文章是题为“纤维化和心肌重塑”的特刊的一部分。
Cardiac fibroblasts help maintain the normal architecture of the healthy heart and are responsible for scar formation and the healing response to pathological insults. Various genetic, biomechanical, or humoral factors stimulate fibroblasts to become contractile smooth muscle-like cells called myofibroblasts that secrete large amounts of extracellular matrix. Unfortunately, unchecked myofibroblast activation in heart disease leads to pathological fibrosis, which is a major risk factor for the development of cardiac arrhythmias and heart failure. A better understanding of the molecular mechanisms that control fibroblast plasticity and myofibroblast activation is essential to develop novel strategies to specifically target pathological cardiac fibrosis without disrupting the adaptive healing response. This review highlights the major transcriptional mediators of fibroblast origin and function in development and disease. The contribution of the fetal epicardial gene program will be discussed in the context of fibroblast origin in development and following injury, primarily focusing on Tcf21 and C/EBP. We will also highlight the major transcriptional regulatory axes that control fibroblast plasticity in the adult heart, including transforming growth factor β (TGFβ)/Smad signaling, the Rho/myocardin-related transcription factor (MRTF)/serum response factor (SRF) axis, and Calcineurin/transient receptor potential channel (TRP)/nuclear factor of activated T-Cell (NFAT) signaling. Finally, we will discuss recent strategies to divert the fibroblast transcriptional program in an effort to promote cardiomyocyte regeneration. This article is a part of a Special Issue entitled “Fibrosis and Myocardial Remodeling”.