Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation.
Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation.
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DOI：
10.1161/circresaha.120.316958
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发表时间：
2020-07-17
影响因子：
20.1
通讯作者：
Elrod JW
中科院分区：
文献类型：
--
作者：
Gibb AA;Lazaropoulos MP;Elrod JW
心脏纤维化是由常驻心脏成纤维细胞的激活介导的，在损伤或应激反应中，成纤维细胞分化为肌成纤维细胞。虽然肌成纤维细胞的形成是对急性损伤（如心肌梗死）的生理反应，但肌成纤维细胞的持续存在，如心力衰竭时，会导致适应性重构不良和进行性功能下降。虽然传统的激活途径，如转化生长因子β (TGFβ)和血管紧张素II (AngII)，已经被很好地表征，但对线粒体功能和细胞代谢的改变却知之甚少，而线粒体功能和细胞代谢是启动和维持肌成纤维细胞形成和功能所必需的。在这篇综述中，我们重点介绍了最近的报道，详细介绍了线粒体和代谢机制，这些机制有助于肌成纤维细胞的分化、持久性和功能，希望找到新的治疗靶点来治疗和潜在地逆转组织器官纤维化。
Cardiac fibrosis is mediated by the activation of resident cardiac fibroblasts, which differentiate into myofibroblasts in response to injury or stress. While myofibroblast formation is a physiological response to acute injury, such as myocardial infarction, myofibroblast persistence, as occurs in heart failure, contributes to maladaptive remodeling and progressive functional decline. While traditional pathways of activation, such as transforming growth factor beta (TGFβ) and angiotensin II (AngII), have been well characterized, less understood are the alterations in mitochondrial function and cellular metabolism that are necessary to initiate and sustain myofibroblast formation and function. In this review, we highlight recent reports detailing the mitochondrial and metabolic mechanisms that contribute to myofibroblast differentiation, persistence and function with the hope of identifying novel therapeutic targets to treat, and potentially reverse, tissue organ fibrosis.