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<p>Liver fibrosis represents a significant clinical challenge. While targeting activated hepatic stellate cells (HSCs) is a promising therapeutic strategy, the specific role of Eukaryotic Translation Initiation Factor 5&#xa0;A (EIF5A) in this process remains incompletely understood. EIF5A expression was analyzed in human fibrotic liver specimens and experimental mouse models. Its therapeutic potential was evaluated through pharmacological inhibition in fibrotic mice. Direct effects and mechanisms on HSCs were further investigated in vitro, with a focus on mitochondrial function. Immunostaining revealed a marked increase of EIF5A in activated HSCs from human fibrotic livers, which was consistent with findings in mice. Inhibition of EIF5A significantly attenuated liver fibrosis in vivo. Mechanistically, EIF5A deficiency directly impaired mitochondrial function in HSCs, leading to reduced ATP production, decreased mitochondrial membrane potential, and abnormal mitochondrial morphology, thereby suppressing their activation. Our results indicate that EIF5A contributes to HSC activation during liver fibrosis, in part through modulating mitochondrial bioenergetics. The concordant observations in human and mouse systems highlight the translational relevance of EIF5A, supporting its further investigation as a potential therapeutic target for liver fibrosis.</p>

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Targeting EIF5A suppresses liver fibrosis through impairment of mitochondrial function in hepatic stellate cells

  • 期刊论文

  • 发表日期：

    2026年2月23日

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  • Yuzhu Di,
  • Lubo Jin,
  • Xiaoyu Zhang,
  • Pengchao Deng,
  • Feiyang Gao,
  • Shizhu Jin

摘要

Liver fibrosis represents a significant clinical challenge. While targeting activated hepatic stellate cells (HSCs) is a promising therapeutic strategy, the specific role of Eukaryotic Translation Initiation Factor 5 A (EIF5A) in this process remains incompletely understood. EIF5A expression was analyzed in human fibrotic liver specimens and experimental mouse models. Its therapeutic potential was evaluated through pharmacological inhibition in fibrotic mice. Direct effects and mechanisms on HSCs were further investigated in vitro, with a focus on mitochondrial function. Immunostaining revealed a marked increase of EIF5A in activated HSCs from human fibrotic livers, which was consistent with findings in mice. Inhibition of EIF5A significantly attenuated liver fibrosis in vivo. Mechanistically, EIF5A deficiency directly impaired mitochondrial function in HSCs, leading to reduced ATP production, decreased mitochondrial membrane potential, and abnormal mitochondrial morphology, thereby suppressing their activation. Our results indicate that EIF5A contributes to HSC activation during liver fibrosis, in part through modulating mitochondrial bioenergetics. The concordant observations in human and mouse systems highlight the translational relevance of EIF5A, supporting its further investigation as a potential therapeutic target for liver fibrosis.