Knockdown of suppressor of glucose by autophagy (SOGA1) alleviates the progression of non-alcoholic steatohepatitis (NASH) by reducing hepatocyte senescence through regulating AMPK/mTOR-mediated mitoc
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- #NASH
- #Hepatocyte Senescence
- #SOGA1
- Knockdown of SOGA1 reduces progression of non-alcoholic steatohepatitis (NASH) in mice by lowering inflammation, fibrosis, and hepatocyte senescence.
- Silencing SOGA1 in hepatocytes decreases inflammatory cytokines (TNF-α, IL-6), fibrosis markers (α-SMA, COL1A1, TGF-β1), and senescence markers (p53, p21, γ-H2AX).
- SOGA1 suppression enhances AMPK/mTOR pathway activation and mitochondrial homeostasis, increasing mitophagy and reducing mitochondrial fusion.
- Conditioned medium from SOGA1-silenced hepatocytes inhibits activation and collagen production in hepatic stellate cells, slowing fibrosis.
- Mechanistically, SOGA1 recruits RNF41 to inhibit AMPK/mTOR, impairing mitophagy and promoting hepatocyte senescence, which activates stellate cells via IL-6.
- In vivo lentiviral knockdown of SOGA1 alleviates NASH symptoms in mouse models, supporting its potential as a therapeutic target.