Metabolic requirements of pulmonary fibrosis: role of fibroblast metabolism.
Metabolic requirements of pulmonary fibrosis: role of fibroblast metabolism.
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DOI：
10.1111/febs.15693
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Mutlu GM
中科院分区：
文献类型：
--
作者：
Hamanaka RB;Mutlu GM
纤维化是一种病理状态，其特征在于细胞外基质的过度沉积和慢性瘢痕形成，可以影响每个器官系统。器官纤维化与显著的发病率和死亡率相关，在发达国家占所有死亡的45%。在肺部，许多慢性肺部疾病可能导致纤维化，最具破坏性的是特发性肺纤维化（IPF），其影响全球约300万人，中位生存期为3.8年。目前批准的IPF疗法不能显著延长寿命，因此迫切需要新的治疗策略来治疗IPF和其他纤维化疾病。肺纤维化的核心是肌成纤维细胞，即具有成纤维细胞和平滑肌细胞特征的收缩细胞，其是纤维化疾病中负责基质沉积的主要细胞类型。许多工作都集中在靶向细胞外生长因子和细胞内信号调节肌成纤维细胞分化。最近，与肌成纤维细胞分化相关的代谢变化已经成为肌成纤维细胞功能所需的靶向机制。在这篇综述中，我们将讨论与肌成纤维细胞分化相关的代谢变化，以及这些变化促进肌成纤维细胞功能的机制。然后，我们将讨论这一新知识的潜力，以导致IPF和其他纤维化疾病的新疗法的开发。响应于改变的局部生长因子和机械信号，肺成纤维细胞分化成肌成纤维细胞，肌成纤维细胞是负责与特发性肺纤维化（IPF）相关的慢性瘢痕形成和器官功能丧失的关键细胞。最近的研究表明，肌成纤维细胞分化与代谢重编程有关，代谢重编程支持这些细胞的收缩性、基质产生性。这些代谢改变可能为IPF和其他纤维化疾病的治疗提供新的靶点。
Fibrosis is a pathologic condition characterized by excessive deposition of extracellular matrix and chronic scaring that can affect every organ system. Organ fibrosis is associated with significant morbidity and mortality, contributing to as many as 45% of all deaths in the developed world. In the lung, many chronic lung diseases may lead to fibrosis, the most devastating being idiopathic pulmonary fibrosis (IPF), which affects approximately 3 million people worldwide and has a median survival of 3.8 years. Currently approved therapies for IPF do not significantly extend lifespan and thus, there is pressing need for novel therapeutic strategies to treat IPF and other fibrotic diseases. At the heart of pulmonary fibrosis are myofibroblasts, contractile cells with characteristics of both fibroblasts and smooth muscle cells, which are the primary cell type responsible for matrix deposition in fibrotic diseases. Much work has centered around targeting the extracellular growth factors and intracellular signaling regulators of myofibroblast differentiation. Recently, metabolic changes associated with myofibroblast differentiation have come to the fore as targetable mechanisms required for myofibroblast function. In this review we will discuss the metabolic changes associated with myofibroblast differentiation, as well as the mechanisms by which these changes promote myofibroblast function. We will then discuss the potential for this new knowledge to lead to development of novel therapies for IPF and other fibrotic diseases. In response to altered local growth factor and mechanical signals, lung fibroblasts differentiate into myofibroblasts, the key cells responsible for the chronic scaring and loss of organ function associated with Idiopathic Pulmonary Fibrosis (IPF). Recent work has shown that myofibroblast differentiation is associated with metabolic reprogramming that supports the contractile, matrix-producing nature of these cells. These metabolic alterations may provide novel targets for treatment of IPF and other fibrotic diseases.
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影响因子：
3.7
作者：
Aoki, Yasuhiro;Maeno, Toshitaka;Kurabayashi, Masahiko
通讯作者：
Kurabayashi, Masahiko
影响因子：
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作者：
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通讯作者：
HARDIE, DG
DOI：
10.1165/rcmb.2019-0051oc
发表时间：
2019-10-01
影响因子：
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作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Leof, Edward B.
DOI：
10.1152/ajplung.00165.2013
发表时间：
2013-11-01
影响因子：
4.9
作者：
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通讯作者：
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