Zank Daniel C, Bueno Marta, Mora Ana L, Rojas Mauricio
Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Front Med (Lausanne). 2018 Feb 5;5:10. doi: 10.3389/fmed.2018.00010. eCollection 2018.
At present, the etiology of idiopathic pulmonary fibrosis (IPF) remains elusive. Over the past two decades, however, researchers have identified and described the underlying processes that result in metabolic dysregulation, metabolic reprogramming, and mitochondrial dysfunction observed in the cells of IPF lungs. Metabolic changes and mitochondrial dysfunction in IPF include decreased efficiency of electron transport chain function with increasing production of reactive oxygen species, decreased mitochondrial biogenesis, and impaired mitochondrial macroautophagy, a key pathway for the removal of dysfunctional mitochondria. Metabolic changes in IPF have potential impact on lung cell function, differentiation, and activation of fibrotic responses. These alterations result in activation of TGF-β and predispose to the development of pulmonary fibrosis. IPF is a disease of the aged, and many of these same bioenergetic changes are present to a lesser extent with normal aging, raising the possibility that these anticipated alterations in metabolic processes play important roles in creating susceptibility to the development of IPF. This review explores what is known regarding the cellular metabolic and mitochondrial changes that are found in IPF, and examines this body of literature to identify future research direction and potential points of intervention in the pathogenesis of IPF.
目前，特发性肺纤维化（IPF）的病因仍不清楚。然而，在过去二十年中，研究人员已经识别并描述了导致IPF肺细胞中代谢失调、代谢重编程和线粒体功能障碍的潜在过程。IPF中的代谢变化和线粒体功能障碍包括电子传递链功能效率降低，活性氧生成增加，线粒体生物合成减少，以及线粒体巨自噬受损，线粒体巨自噬是清除功能失调线粒体的关键途径。IPF中的代谢变化对肺细胞功能、分化和纤维化反应的激活具有潜在影响。这些改变导致转化生长因子-β（TGF-β）激活，并易引发肺纤维化。IPF是一种老年疾病，许多相同的生物能量变化在正常衰老过程中也会在较小程度上出现，这增加了这些预期的代谢过程改变在导致IPF易感性方面发挥重要作用的可能性。本综述探讨了关于IPF中发现的细胞代谢和线粒体变化的已知情况，并审视了这一系列文献，以确定未来的研究方向以及IPF发病机制中的潜在干预点。
