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A "Cocktail" Fluorescent Probe for Multi-ROS Imaging Unveils Ferroptosis-Driven Liver Fibrosis Development

  • 0College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan, Shandong, 250014, P.R. China.
Angewandte Chemie +

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June 27, 2025

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June 27, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Reactive oxygen species (ROS) link ferroptosis and liver fibrosis. A novel probe, FP-ROS, revealed a pathway where ROS and ferroptosis drive hepatic stellate cell activation, offering new therapeutic targets.

Area Of Science

  • Hepatology
  • Molecular Biology
  • Biochemistry

Background

  • Liver fibrosis is a chronic liver injury response with no targeted therapies.
  • The role of ferroptosis in liver fibrosis remains controversial.
  • Reactive oxygen species (ROS) may link ferroptosis and liver fibrosis.

Purpose Of The Study

  • To elucidate the molecular network of ROS and ferroptosis in liver fibrosis.
  • To develop a tool for simultaneous imaging of key ROS species.
  • To investigate the role of ferroptosis in hepatic stellate cell activation.

Main Methods

  • Design and synthesis of a multi-functional fluorescence probe (FP-ROS) for O2•−, H2O2, and ONOO− imaging.
  • Assessment of ferroptosis levels in drug-treated fibrosis mouse livers.
  • Transcriptomic and proteomic analyses to identify signaling pathways.

Main Results

  • FP-ROS enabled sensitive and selective simultaneous imaging of O2•−, H2O2, and ONOO−.
  • A novel signaling pathway (NOX→ONOO−→GCLM(C46)→GSH→ferroptosis→HSCs activation) was elucidated.
  • Ferroptosis was demonstrated to play a critical role in hepatic stellate cell activation.

Conclusions

  • Ferroptosis is a key driver of hepatic stellate cell activation in liver fibrosis.
  • The study clarifies the molecular interplay between ROS and ferroptosis in fibrosis progression.
  • Findings offer novel insights for liver fibrosis diagnosis and therapy.

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