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Can Nrf2 Modulate the Development of Intestinal Fibrosis and Cancer in Inflammatory Bowel Disease?
Simona Pompili1, Roberta Sferra1, Eugenio Gaudio2
1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Abstract:
One of the main mechanisms carried out by the cells to counteract several forms of stress is the activation of the nuclear factor erythroid 2-related factor (Nrf2) signaling. Nrf2 signaling controls the expression of many genes through the binding of a specific cis-acting element known as the antioxidant response element (ARE). Activation of Nrf2/ARE signaling can mitigate several pathologic mechanisms associated with an autoimmune response, digestive and metabolic disorders, as well as respiratory, cardiovascular, and neurodegenerative diseases. Indeed, several studies have demonstrated that Nrf2 pathway plays a key role in inflammation and in cancer development in many organs, including the intestine. Nrf2 appears to be involved in inflammatory bowel disease (IBD), an immune-mediated chronic and disabling disease, with a high risk of developing intestinal fibrotic strictures and cancer. Currently, drugs able to increase cytoprotective Nrf2 function are in clinical trials or already being used in clinical practice to reduce the progression of some degenerative conditions. The role of Nrf2 in cancer development and progression is controversial, and drugs able to inhibit abnormal levels of Nrf2 are also under investigation. The goal of this review is to analyze and discuss Nrf2-dependent signals in the initiation and progression of intestinal fibrosis and cancers occurring in IBD.
Insights
The nuclear factor erythroid 2-related factor (Nrf2) pathway regulates cellular stress responses and is implicated in inflammatory bowel disease (IBD). This review examines Nrf2
Area of Science:
- Cellular Biology
- Molecular Biology
- Gastroenterology
Background:
- Cellular stress responses are often mediated by the nuclear factor erythroid 2-related factor (Nrf2) signaling pathway.
- Nrf2 controls gene expression via the antioxidant response element (ARE) and impacts various diseases, including inflammatory bowel disease (IBD).
- The Nrf2 pathway's role in IBD pathogenesis, particularly in fibrosis and cancer development, requires further investigation.
Purpose of the Study:
- To review and discuss the role of Nrf2-dependent signals in the initiation and progression of intestinal fibrosis and cancers associated with IBD.
Main Methods:
- Literature review and analysis of existing studies on Nrf2 signaling in the context of IBD, intestinal fibrosis, and cancer.
Main Results:
- Nrf2 activation can mitigate pathological mechanisms in various diseases, including autoimmune, metabolic, and cardiovascular conditions.
- The Nrf2 pathway is crucial in inflammation and cancer development across multiple organs, including the intestine.
- Nrf2's role in IBD is significant, contributing to fibrotic strictures and cancer risk, though its precise function in cancer progression is debated.
Conclusions:
- Understanding Nrf2's dual role in IBD is critical for developing targeted therapies.
- Modulating Nrf2 activity presents potential therapeutic strategies for IBD-related complications, including fibrosis and cancer.
- Further research is needed to clarify the controversial aspects of Nrf2 in cancer development and progression within the context of IBD.
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