Related Experiment Video
Updated: Oct 2, 2025
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
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.
Abstract:
Oxidative stress is the leading cause of most liver diseases, such as drug-induced liver injury, viral hepatitis, and alcoholic hepatitis caused by drugs, viruses, and ethanol. The Kelch-like ECH-associated protein 1-NFE2-related factor 2 (Keap1-Nrf2) system is a critical defense mechanism of cells and organisms in response to oxidative stress. Accelerating studies have clarified that the Keap1-Nrf2 axis are involved in the prevention and attenuation of liver injury. Nrf2 up-regulation could alleviate drug-induced liver injury in mice. Moreover, many natural Nrf2 activators can regulate lipid metabolism and oxidative stress of liver cells to alleviate fatty liver disease in mice. In virus hepatitis, the increased Nrf2 can inhibit hepatitis C viral replication by up-regulating hemeoxygenase-1. In autoimmune liver diseases, the increased Nrf2 is essential for mice to resist liver injury. In liver cirrhosis, the enhanced Nrf2 reduces the activation of hepatic stellate cells by reducing reactive oxygen species levels to prevent liver fibrosis. Nrf2 plays a dual function in liver cancer progression. At present, a Nrf2 agonist has received clinical approval. Therefore, activating the Nrf2 pathway to induce the expression of cytoprotective genes is a potential option for treating liver diseases. In this review, we comprehensively summarized the relationships between oxidative stress and liver injury, and the critical role of the Nrf2 pathway in multiple liver diseases.
Insights
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.
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.
More Related Videos
08:41Novel In Vivo Micro-Computed Tomography Imaging Techniques for Assessing the Progression of Non-Alcoholic Fatty Liver Disease
Published on: March 24, 2023
08:35A Model of Experimental Steatosis In Vitro: Hepatocyte Cell Culture in Lipid Overload-Conditioned Medium
Published on: May 18, 2021
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:31Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:24Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
01:26Diseases of the Liver and Gallbladder
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
01:30Liver Physiology
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...