Myofibroblasts: Trust your heart and let fate decide

被引:257
作者
Davis, Jennifer [1 ]
Molkentin, Jeffery D. [1 ,2 ]
机构
[1] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA
[2] Howard Hughes Med Inst, Cincinnati, OH 45229 USA
基金
美国国家卫生研究院;
关键词
Fibrosis; Extracellular matrix; TGF beta; Angiotensin II; Serum response factor; TRP channel; SERUM-RESPONSE FACTOR; SMOOTH-MUSCLE ACTIN; GROWTH-FACTOR-BETA; PROTEIN-KINASE ACTIVATION; IMPROVES CARDIAC-FUNCTION; EPICARDIUM-DERIVED CELLS; TGF-BETA; EXTRACELLULAR-MATRIX; MYOCARDIAL FIBROSIS; GENE-EXPRESSION;
D O I
10.1016/j.yjmcc.2013.10.019
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cardiac fibrosis is a substantial problem in managing multiple forms of heart disease. Fibrosis results from an unrestrained tissue repair process orchestrated predominantly by the myofibroblast. These are highly specialized cells characterized by their ability to secrete extracellular matrix (ECM) components and remodel tissue -due to their contractile properties. This contractile activity of the myofibroblast is ascribed, in part, to the expression of smooth muscle alpha-actin (alpha SMA) and other tension-associated structural genes. Myofibroblasts are a newly generated cell type derived largely from residing mesenchymal cells in response to both mechanical and neurohumoral stimuli. Several cytolcines, chemokines, and growth factors are induced in the injured heart, and in conjunction with elevated wall tension, specific signaling pathways and downstream effectors are mobilized to initiate myofibroblast differentiation. Here we will review the cell fates that contribute to the myofibroblast as well as nodal molecular signaling effectors that promote their differentiation and activity. We will discuss canonical versus non-canonical transforming growth factor-beta (TGF beta), angiotensin II (AngII), endothelin-1 (ET-1), serum response factor (SRF), transient receptor potential (TRP) channels, mitogen-activated protein kinases (MAPKs) and mechanical signaling pathways that are required for myofibroblast transformation and fibrotic disease. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium ". (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:9 / 18
页数:10
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