IFRD1 orchestrates hepatocyte metabolism and macrophage interactions to facilitate liver regeneration - PubMed
4 hours ago
- #Metabolic-Immune Crosstalk
- #Liver Regeneration
- #IFRD1
- IFRD1 plays a crucial role in liver regeneration by orchestrating hepatocyte metabolism and macrophage interactions.
- Hepatocyte IFRD1 is rapidly induced during early liver regeneration in mice but decreases in human chronic liver disease.
- Loss of IFRD1 impairs liver repair, while overexpression enhances regeneration in various injury models.
- IFRD1 sustains hepatocyte β-oxidation and mitochondrial ATP production by stabilizing SLC25A5, competing with the E3 ubiquitin ligase TRIM21.
- Increased ATP from IFRD1 activity enables chromatin remodeling in hepatocytes, promoting chemokine expression to recruit CCR2+ monocytes and expand regenerative GPNMB+ macrophages.
- IFRD1 overexpression restores liver regenerative capacity in models of metabolic dysfunction-associated steatohepatitis and liver fibrosis.
- The study highlights the therapeutic potential of targeting IFRD1 to enhance liver regeneration in disease contexts.