Early-activated extracellular matrix proteins shape the metabolic and spatial dynamics of the kidney fibrotic microenvironment - PubMed
3 hours ago
- #kidney fibrosis
- #ECM1
- #mitochondrial reprogramming
- Early-activated extracellular matrix protein ECM1 plays a crucial role in kidney fibrosis.
- ECM1 knockout mice develop spontaneous fibrosis and early death, while ECM1 levels increase in chronic kidney disease.
- Targeting ECM1 reduces renal fibrosis by disrupting the integrin α2β1-RhoC axis and suppressing YAP activity.
- Reduced YAP activity enhances mitochondrial oxidative phosphorylation (OXPHOS) and promotes tissue repair.
- Spatial transcriptomics and proteomics reveal mitochondrial reprogramming in tubules that counteracts fibrosis.
- YAP inactivation in fibroblasts limits aberrant activation without impairing their OXPHOS.
- The study uncovers a mechano-metabolic pathway where mitochondrial shifts defend against kidney fibrosis.