AI Article Synopsis
- Nrf2 is important for regulating how cells deal with oxidative stress, and its overactivation due to the loss of Keap1 can lead to severe health issues in mice.
- Removing Nrf2 from the oesophagus in Keap1-null mice allows them to survive but leads to kidney problems, such as polyuria and hydronephrosis, due to lower levels of aquaporin 2, which is crucial for water reabsorption.
- The study indicates that controlling Nrf2 activity during development is essential for kidney health and suggests that specific ablation of Nrf2 could help create animal models to explore new functions of this protein.
Article Abstract
NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333130 | PMC |
| http://dx.doi.org/10.1038/ncomms14577 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!