Metabolic dysfunction and inflammatory disease: the role of stromal fibroblasts. (17th December 2020) - Farah, Hussein
Abstract : Mesenchymal stromal fibroblasts have emerged as key mediators of the inflammatory response and drivers of localised inflammation, in part through their interactions with resident and circulating immune cells at inflammatory sites. As such, they have been implicated in a number of chronic inflammatory conditions as well as in tumour progression through modifying the microenvironment. The connection between metabolic changes and altered phenotype of fibroblasts in inflammatory microenvironments has clear implications for our understanding of how chronic inflammation is regulated and for the development of new anti‐inflammatory therapeutics. In this review, we consider the evidence that changes to fibroblast metabolic state underpin chronic inflammation. We examine recent research on fibroblast metabolism in inflammatory microenvironments and consider their involvement in inflammation, providing insight into the role of fibroblasts and metabolism in mediating inflammatory disease progression namely cancer, arthritis and fibrotic disorders including chronic kidney disease, pulmonary fibrosis, heart disease and liver disease. Abstract : Stromal fibroblasts are central mediators of chronic inflammatory disease. Changes to fibroblast metabolism (including glycolysis, oxidative phosphorylation, pentose phosphate pathway, glutamine metabolism and lactate transport) fuels and underpins the switch in fibroblast phenotype towards an inflammatory‐activated phenotype that drives chronic inflammation. Cancer‐associated fibroblasts drive tumour progression, activated synoviocytes drive joint inflammation, and activated myoblasts drive fibrotic disorders including chronic kidney disease, pulmonary fibrosis, heart disease and liver disease.