Lipotoxic hepatocyte-derived UBQLN1-enriched small extracellular vesicles activate hepatic stellate cells to promote hepatic fibrosis - PubMed
5 days ago
- #MASH
- #UBQLN1
- #fibrosis
- UBQLN1 levels are significantly elevated in serum and serum-derived small extracellular vesicles (sEVs) from MASH patients, showing high diagnostic accuracy.
- Lipotoxic stress induces O-GlcNAcylation at the T277 site of UBQLN1 via OGT, reducing its ubiquitin-mediated degradation.
- Hepatocyte UBQLN1 facilitates sEV secretion by regulating LAMP1-mediated fusion of multivesicular bodies (MVBs) with lysosomes.
- sEVs containing UBQLN1 activate hepatic stellate cells by degrading ATP6V1B2, inhibiting lysosomal acidification and mitophagy.
- Hepatic-specific knockdown of Ubqln1 or Ogt alleviates fibrosis and metabolic disorders in MASH mice.
- UBQLN1's post-translational modification plays a critical role in MASH progression and offers potential as a therapeutic target.