Abstract: FR-PO307
Inhibition of p53 Ameliorates Adenine-Induced Kidney Injury in Mice
Session Information
- Diabetic Kidney Disease: Basic - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Lee, Hak Joo, University of Texas Health San Antonio, San Antonio, Texas, United States
- Zhang, Guanshi, University of Texas Health San Antonio, San Antonio, Texas, United States
- Montellano, Richard, University of Texas Health San Antonio, San Antonio, Texas, United States
- Tamayo, Ian M., University of Texas Health San Antonio, San Antonio, Texas, United States
- Trevino, Esmeralda, University of Texas Health San Antonio, San Antonio, Texas, United States
- Bopassa, Jean C., University of Texas Health San Antonio, San Antonio, Texas, United States
- Md, David Gius, University of Texas Health San Antonio, San Antonio, Texas, United States
- Sharma, Kumar, University of Texas Health San Antonio, San Antonio, Texas, United States
Group or Team Name
- Center for Precision Medicine.
Background
Diabetes is associated with premature senescence and an increase in apoptosis in the kidney of patients with diabetes in association with upregulation of p53. In addition, inhibition of production of the endogenous nephrotoxic metabolite adenine ameliorated diabetes-induced kidney injury in mice with type 2 diabetes and adenine has been found to stimulate the senescence associated secretory phenotype (SASP) including p21 mRNA expression in the kidney of WT mice. We therefore hypothesized that deletion of p53 ameliorates adenine-induced kidney injury by inhibiting p21-apoptosis pathway in mice.
Methods
We randomized 8-10 weeks age of p53KO and WT male mice. Mice received 0.2 % adenine-containing diet or normal chow for 4 weeks (n=5-12 per group).
Results
Adenine decreased body weight, blood glucose level, and kidney, liver, and heart weight to tibia length ratio in WT and p53KO mice. p53KO significantly reduced adenine-induced albuminuria, kidney fibronectin accumulation and plasma blood urea nitrogen increment in mice. However p53KO did not affect adenine-increased kidney injury molecules-1 level in the kidney. Adenine increased mRNA expression of SASP in the kidney of both WT and p53KO mice. p53KO significantly decreased adenine induced IL-6 and partially reduced other SASP components (p16, TGFβ1, and IL-1β). p53KO inhibited adenine-induced p21 mRNA expression and degradation of Bcl2.
Conclusion
Our data suggest that the adenine-p53-apoptosis pathway contributes to kidney injury in mice. Adenine-p53 axis could be used for a therapeutic target of diabetes kidney disease and other kidney diseases characterized by adenine excess production.