Comparative non-targeted LC-MS metabolomic profiling of murine bone marrow-derived macrophages cultured in 2D versus 3D

ABSTRACT:

Macrophages are key drivers of inflammatory and fibrotic diseases and their activation is shaped by interactions in their tissue microenvironment. However, dissecting the processes that drive immunopathology has proved challenging as traditional 2D culture methods fail to capture the complex molecular environment that macrophages inhabit in vivo. To address this, we generated a 3D in vitro model to better mimic the in vivo biophysical microenvironment. We show that the extracellular matrix (ECM) protein vitronectin promotes a novel pro-fibrotic macrophage phenotype in 3D that is characterised by increased expression of the NAD+ ectoenzyme CD38, elevated glycolysis and mitochondrial metabolism, and synthesis of the immunomodulatory metabolite itaconate. This is validated in vivo where vitronectin-deficient mice were protected from an experimental model of idiopathic pulmonary fibrosis. Thus, we uncover a novel link between the composition of tissue niches and macrophage pro-fibrotic function via altered metabolic reprogramming. 

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS12917 | MetaboLights | 2026-06-08

REPOSITORIES: MetaboLights