Internal medicine

Pathology

Idiopathic pulmonary fibrosis

Disease

Fibrosis

Bioinformatics

Biology

Extracellular matrix

Cirrhosis

Lung

Steatohepatitis

Fatty liver

Pulmonary fibrosis

Cell biology

Medicine

Nature Reviews Drug Discovery

Fibrosis is the abnormal deposition of extracellular matrix, which can lead to organ dysfunction, morbidity, and death. The disease burden caused by fibrosis is substantial, and there are currently no therapies that can prevent or reverse fibrosis. Metabolic alterations are increasingly recognized as an important pathogenic process that underlies fibrosis across many organ types. As a result, metabolically targeted therapies could become important strategies for fibrosis reduction. Indeed, some of the pathways targeted by antifibrotic drugs in development — such as the activation of transforming growth factor-β and the deposition of extracellular matrix — have metabolic implications. This Review summarizes the evidence to date and describes novel opportunities for the discovery and development of drugs for metabolic reprogramming, their associated challenges, and their utility in reducing fibrosis. Fibrotic therapies are potentially relevant to numerous common diseases such as cirrhosis, non-alcoholic steatohepatitis, chronic renal disease, heart failure, diabetes, idiopathic pulmonary fibrosis, and scleroderma. Fibrosis features in numerous chronic diseases, such as non-alcoholic steatohepatitis and heart failure, and no existing therapies can prevent or reverse this abnormal deposition of extracellular matrix, which leads to organ dysfunction. Here, Liu and colleagues describe how this energy-intensive process could be targeted by therapies that interfere with metabolism, including the metabolic implications of drugs directed at transforming growth factor-β and the deposition of extracellular matrix.

Targeting metabolic dysregulation for fibrosis therapy