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Related Experiment Video

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The Nrf2 Pathway in Liver Diseases.

Jiaming Zhou1, Qiuxian Zheng1, Zhi Chen1

  • 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Frontiers in Cell and Developmental Biology
|February 28, 2022
PubMed
Summary

The Kelch-like ECH-associated protein 1-NFE2-related factor 2 (Keap1-Nrf2) pathway protects against oxidative stress and liver injury. Activating this pathway offers a promising therapeutic strategy for various liver diseases.

Keywords:
kelch-like ECH-associated protein 1liver diseasesnuclear factor-erythroid 2-related factor 2oxidative stressreactive oxygen species

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Area of Science:

  • Hepatology
  • Molecular Biology
  • Oxidative Stress Research

Background:

  • Oxidative stress is a primary driver of diverse liver diseases, including drug-induced, viral, and alcoholic hepatitis.
  • The Keap1-Nrf2 system serves as a crucial cellular defense against oxidative stress, playing a significant role in liver health.

Purpose of the Study:

  • To review the intricate relationship between oxidative stress and liver injury.
  • To elucidate the pivotal role of the Keap1-Nrf2 pathway in mitigating various liver diseases.

Main Methods:

  • Literature review of studies investigating oxidative stress and the Keap1-Nrf2 pathway in liver disease models.
  • Analysis of research on Nrf2 activators and their effects on liver cell metabolism and injury.

Main Results:

  • Nrf2 up-regulation demonstrates protective effects against drug-induced liver injury and fatty liver disease in mice.
  • Enhanced Nrf2 activity inhibits hepatitis C viral replication and is essential for resisting injury in autoimmune liver diseases.
  • Nrf2 activation reduces hepatic stellate cell activation and liver fibrosis in cirrhosis, though it has a dual role in liver cancer.

Conclusions:

  • The Keap1-Nrf2 pathway is a key regulator in preventing and attenuating liver injury across multiple disease contexts.
  • Targeting the Nrf2 pathway to induce cytoprotective genes presents a viable therapeutic approach for liver diseases.