Title: Metabolic requirements of pulmonary fibrosis: role of fibroblast metabolism.

Authors: Hamanaka, Robert B; Mutlu, Gökhan M

Published In FEBS J, (2021 11)

Abstract: 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 the development of novel therapies for IPF and other fibrotic diseases.

PubMed ID: 33393204

MeSH Terms: Animals; Fibroblasts/metabolism*; Fibrosis/metabolism*; Humans