Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis

Lin, Lifan; Li, Xinmiao; Li, Yifei; Lang, Zhichao; Li, Yeping; Zheng, Jianjian

doi:10.1016/j.jpha.2023.11.009

Cited by 7 publications

(1 citation statement)

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“…Research indicates that Beclin1 facilitates ferroptosis through direct binding to SLC7A11 and suppressing its activity [38]. Lin L et al [39] demonstrated that ginsenoside Rb1 (GRb1) triggers hepatic stellate cell ferroptosis by acting on the BECN1/SLC7A11 axis to mitigate liver fibrosis. In a separate study, Liu J et al [40] discovered that activation of the Nrf2 signaling pathway can inhibit ferroptosis by inducing autophagy to interfere with the engagement of SLC7A11 and BECN1, thereby promoting the membrane translocation of SLC7A11 and the synthesis of GSH.…”

Section: Discussionmentioning

confidence: 99%

SLC7A11 Silencing Modulates Ferroptosis and Autophagy to Reduce Sodium Arsenite-Induced Activation of Hepatic Stellate Cells

Ding,

Zhao,

Huang

et al. 2024

Preprint

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Arsenic is a prevalent environmental pollutant with recognized carcinogenic properties. Liver fibrosis is a frequent consequence of arsenic poisoning, with the activation of hepatic stellate cells (HSCs) being a central event. Solute Carrier Family 7 Member 11 (SLC7A11), a pivotal regulator of ferroptosis, may be involved in the process of arsenic-induced liver fibrosis. This study utilized lentiviral vector-mediated SLC7A11 silencing in LX-2 cells (a type of human hepatic stellate cells) to establish an SLC7A11 knockout cell model, which was then exposed to sodium arsenite (NaAsO2). Protein interactions were assessed through Protein Immunoprecipitation (IP), and protein levels were evaluated via Western blot analysis. It was found that NaAsO2 decreased cellular Fe2+ levels and nuclear receptor co-activator 4 (NCOA4) expression, with SLC7A11 silencing reversing these effects. Additionally, IP analysis revealed an interaction between Beclin1 and SLC7A11 proteins in LX-2 cells exposed to NaAsO2. Silencing SLC7A11 attenuated the reduction in Tumor Protein p53(P53), and p-mammalian target of rapamycin (p-mTOR) protein levels, along with the rise in Beclin1, Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), α-smooth muscle actin (α-SMA) and Fibroblast activation protein-α (FAP) induced by NaAsO2. Consequently, SLC7A11 silencing promoted cellular ferroptosis, reduced autophagy levels through the P53/AMPK/mTOR pathway, and inhibited HSC activation by NaAsO2, potentially mitigating liver fibrosis.

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Section: Discussionmentioning

confidence: 99%