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Interactions between BdkrB2 and p53 genes in the developing kidney
Samir S El-Dahr1, Zubaida Saifudeen
1Tulane University School of Medicine, Department of Pediatrics, Section of Pediatric Nephrology, New Orleans, LA 70112, USA. seldahr@tulane.edu
Biological Chemistry
|November 16, 2012
Summary
Gene-environment interactions cause congenital disorders. We found that bradykinin B2 receptor (BdkrB2) and p53 gene interactions in developing kidneys lead to renal dysgenesis under salt stress.
Area of Science:
- Developmental biology
- Molecular genetics
- Renal physiology
Background:
- Congenital disorders often arise from gene-environment interactions, necessitating relevant animal models.
- Genetic interactions between the bradykinin B2 receptor (BdkrB2) and the p53 tumor suppressor are crucial in kidney development.
Purpose of the Study:
- To investigate the mechanistic link between BdkrB2, p53, and renal dysgenesis under gestational salt stress.
- To elucidate the functional cross-talk between BdkrB2 and p53 in the developing kidney.
Main Methods:
- Utilized a Bdkrb2(-/-) mouse model exposed to gestational salt stress.
- Analyzed p53 stabilization, apoptosis, and gene expression patterns.
- Investigated the role of checkpoint kinase 1 (Chk1) in p53 phosphorylation.
Main Results:
- Bdkrb2(-/-) embryos under salt stress exhibited renal dysgenesis.
- This phenotype was mediated by p53 stabilization, apoptosis, and repressed epithelial differentiation.
- A novel cross-talk was identified: BdkrB2 is a p53 transcriptional target, and its inactivation upregulates Chk1, enhancing p53 phosphorylation.
Conclusions:
- Gestational salt stress combined with BdkrB2 deficiency triggers a p53-mediated pathway leading to renal dysgenesis.
- The interplay between BdkrB2, p53, and Chk1 is critical for normal kidney development and presents a potential therapeutic target.
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