Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context.

ABSTRACT: Fibrosis is a progressive biological condition, leading to organ dysfunction in various clinical settings. Although fibroblasts and macrophages are known as key cellular players for fibrosis development, a comprehensive functional model that considers their interaction in the metabolic/immunologic context of fibrotic tissue has not been set up. Here we show, by transcriptome-based mathematical modeling in an in vitro system that represents macrophage-fibroblast interplay and reflects the functional effects of inflammation, hypoxia and the adaptive immune context, that irreversible fibrosis development is associated with specific combinations of metabolic and inflammatory cues. The in vitro signatures are in good alignment with transcriptomic profiles generated on laser captured glomeruli a

SUBMITTER: Setten E 

PROVIDER: S-EPMC9618579 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature