Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria.
Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria.
Pharmacol Ther. 2023 Jun;246:108436. doi: 10.1016/j.pharmthera.2023.108436. Epub 2023 May 5.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder of unknown origin and the most common interstitial lung disease. It progresses with the recruitment of fibroblasts and myofibroblasts that contribute to the accumulation of extracellular matrix (ECM) proteins, leading to the loss of compliance and alveolar integrity, compromising the gas exchange capacity of the lung. Moreover, while there are therapeutics available, they do not offer a cure. Thus, there is a pressing need to identify better therapeutic targets. With the advent of transcriptomics, proteomics, and metabolomics, the cellular mechanisms underlying disease progression are better understood. Metabolic homeostasis is one such factor and its dysregulation has been shown to impact the outcome of IPF. Several metabolic pathways involved in the metabolism of lipids, protein and carbohydrates have been implicated in IPF. While metabolites are crucial for the generation of energy, it is now appreciated that metabolites have several non-metabolic roles in regulating cellular processes such as proliferation, signaling, and death among several other functions. Through this review, we succinctly elucidate the role of several metabolic pathways in IPF. Moreover, we also discuss potential therapeutics which target metabolism or metabolic pathways.
特发性肺纤维化(IPF)是一种病因不明的慢性进行性疾病,也是最常见的间质性肺疾病。它的进展伴随着成纤维细胞和肌成纤维细胞的募集,这些细胞有助于细胞外基质(ECM)蛋白的积累,导致顺应性和肺泡完整性丧失,从而损害肺的气体交换能力。此外,尽管有治疗方法可用,但它们并不能治愈疾病。因此,迫切需要确定更好的治疗靶点。随着转录组学、蛋白质组学和代谢组学的出现,疾病进展的细胞机制得到了更好的理解。代谢平衡就是这样一个因素,其失调已被证明会影响 IPF 的结果。涉及脂质、蛋白质和碳水化合物代谢的几种代谢途径与 IPF 有关。虽然代谢物对于产生能量至关重要,但现在人们已经认识到,代谢物在调节细胞过程(如增殖、信号转导和死亡等)中具有几种非代谢作用。通过这篇综述,我们简明扼要地阐述了几种代谢途径在 IPF 中的作用。此外,我们还讨论了针对代谢或代谢途径的潜在治疗方法。