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UBQLN1 Inhibition reduces MASH progression through downregulating SIKE/p38 MAPK pathway in hepatocyte - PubMed

7 hours ago
  • #MASH
  • #p38 MAPK
  • #UBQLN1
  • UBQLN1 inhibition reduces MASH progression by downregulating the SIKE/p38 MAPK pathway in hepatocytes.
  • UBQLN1 is upregulated in MASH patients and mouse models, correlating with hepatic lipid deposition.
  • Knockdown of UBQLN1 reduces hepatic steatosis, inflammation, and fibrosis in MASH mice.
  • UBQLN1 promotes lipid accumulation via ubiquitin-mediated degradation of SIKE, activating the p38 MAPK pathway.
  • RBC-EVs loaded with UBQLN1 siRNA effectively mitigate lipid accumulation and improve MASH progression in vivo.
  • The study identifies the UBQLN1-SIKE-p38 MAPK axis as critical in MASH pathogenesis.
  • A novel RBC-EVs-targeted delivery system is developed for MASH therapy.