4.7 Review

Dysregulation of metabolic pathways in pulmonary fibrosis

Journal

PHARMACOLOGY & THERAPEUTICS
Volume 246, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2023.108436

Keywords

Idiopathic pulmonary fibrosis; Amino acid metabolism; Lipid metabolism; Carbohydrate metabolism; TCA cycle; Therapeutic targets

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder of unknown origin and the most common interstitial lung disease. It is characterized by the accumulation of extracellular matrix (ECM) proteins, leading to compromised lung function. Metabolic dysregulation has been implicated in disease progression, and understanding metabolic pathways in IPF may provide potential therapeutic targets.
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.

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