JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Oxy210 Inhibits Hepatic Expression of Senescence-Associated, Pro-Fibrotic, and Pro-Inflammatory Genes in Mice During Development of MASH and in Hepatocytes In Vitro

  • 0MAX BioPharma Inc., Santa Monica, CA 90404, USA.
Cells +

|

August 13, 2025

|

August 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Oxy210, an anti-fibrotic drug, significantly reduces liver inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH) by inhibiting cellular senescence. This suggests potential therapeutic benefits for MASH and other fibrotic diseases.

Area Of Science

  • Cellular biology
  • Fibrosis research
  • Drug discovery

Background

  • Cellular senescence, a state of irreversible cell cycle arrest, is linked to aging and fibrotic diseases.
  • Transforming growth factor beta (TGF-β) signaling drives senescence and fibrosis in conditions like metabolic dysfunction-associated steatohepatitis (MASH).
  • MASH is a growing global health concern, significantly contributing to liver transplantation needs.

Purpose Of The Study

  • To investigate the role of cellular senescence in MASH pathogenesis.
  • To evaluate the therapeutic potential of Oxy210, an oxysterol-based drug, in a MASH mouse model.
  • To determine if Oxy210 inhibits senescence-associated inflammation and fibrosis.

Main Methods

  • Utilized APOE*3-Leiden.CETP mice, a humanized model for MASH, treated with Oxy210 for 16 weeks.
  • Assessed hepatic inflammation, lipid deposition, fibrosis, atherosclerosis, and adipose tissue inflammation.
  • Investigated senescence-associated gene expression and senescence-associated secretory phenotype (SASP) in mouse liver and HepG2 cells.

Main Results

  • MASH development in mice showed increased hepatic senescence markers and SASP, correlating with pro-fibrotic and pro-inflammatory gene expression.
  • Oxy210 treatment significantly ameliorated MASH hallmarks, including reduced hepatic inflammation and fibrosis.
  • Oxy210 inhibited TGF-β-induced senescence markers and SASP in HepG2 human hepatocytes.

Conclusions

  • Oxy210 demonstrates therapeutic potential for MASH by inhibiting senescence-driven hepatic fibrosis and inflammation.
  • These findings support Oxy210 as a candidate for treating MASH and potentially other senescence-associated fibrotic conditions.

Keywords: