Transient receptor potential (TRP) channels and cardiac fibrosis.
Transient receptor potential (TRP) channels and cardiac fibrosis.
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DOI：
10.2174/1568026611313030005
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发表时间：
2013
影响因子：
3.4
通讯作者：
Yue L
中科院分区：
文献类型：
--
作者：
Yue Z;Zhang Y;Xie J;Jiang J;Yue L
心脏纤维化与大多数心脏疾病有关。纤维化是由心脏成纤维细胞和肌成纤维细胞合成的过量细胞外基质蛋白（ECM）的积聚。成纤维细胞是心脏中最常见的细胞类型，占心脏细胞的75%。肌成纤维细胞几乎不存在于健康的正常心脏组织中，但在患病的心脏中大量出现。心脏成纤维细胞被多种病理刺激激活，例如心肌损伤、氧化应激、机械牵拉和升高的自分泌-旁分泌介质，从而经历增殖、分化成肌成纤维细胞和产生各种细胞因子和ECM蛋白。许多信号通路和生物活性分子参与并协同工作以激活纤维发生级联中的成纤维细胞和肌成纤维细胞。成纤维细胞和肌成纤维细胞不仅是主要的ECM生产者，而且在纤维化心脏病的纤维发生和心肌重塑中起着重要作用。因此，了解心脏成纤维细胞的生物学过程将为纤维化的潜在机制提供新的见解，并为开发抗纤维化药物提供潜在的靶点。最近的研究表明，Ca 2+信号是必不可少的成纤维细胞增殖，分化，和ECM蛋白的生产。本文综述了近年来钙离子信号转导在心脏纤维化发生中的分子机制，以及钙离子通道，特别是瞬时电位（TRP）通道在纤维化心脏病中的作用。TRP通道在心脏成纤维细胞中高度表达。TRPM 7已被证明在TGFβ1介导的纤维形成中是必需的，TRPC 3已被证明在调节成纤维细胞功能中起重要作用。因此，Ca 2+渗透性TRP通道可能成为开发抗纤维化药物的潜在新靶点。
Cardiac fibrosis is associated with most cardiac diseases. Fibrosis is an accumulation of excessive extracellular matrix proteins (ECM) synthesized by cardiac fibroblasts and myofibroblasts. Fibroblasts are the most prevalent cell type in the heart, comprising 75% of cardiac cells. Myofibroblasts are hardly present in healthy normal heart tissue, but appear abundantly in diseased hearts. Cardiac fibroblasts are activated by a variety of pathological stimuli, such as myocardial injury, oxidative stress, mechanical stretch, and elevated autocrine-paracrine mediators, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins. A number of signaling pathways and bioactive molecules are involved and work in concert to activate fibroblasts and myofibroblasts in the fibrogenesis cascade. Fibroblasts and myofibroblasts are not only principal ECM producers, but also play a central role in fibrogenesis and myocardial remodeling in fibrotic heart disease. Thus, understanding the biological processes of cardiac fibroblasts will provide novel insights into the underlying mechanisms of fibrosis and provide potential targets for developing anti-fibrotic drugs. Recent studies demonstrate that Ca2+ signal is essential for fibroblast proliferation, differentiation, and ECM-protein production. This review focuses on the recent advances in understanding molecular mechanisms of Ca2+ signaling in cardiac fibrogenesis, and potential role of Ca2+-permeable channels, in particular, the transient potential (TRP) channels in fibrotic heart disease. TRP channels are highly expressed in cardiac fibroblasts. TRPM7 has been shown to be essential in TGFβ1 mediated fibrogenesis, and TRPC3 has been demonstrated to play an essential role in regulating fibroblast function. Thus, the Ca2+-permeable TRP channels may serve as potential novel targets for developing anti-fibrotic drugs.