Abstract: SA-PO0257
MARY1 Reduces PFKFB3 and Markers of Kidney Fibrosis in Aged Mice
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Mcalister, Kai W., The University of Arizona College of Pharmacy, Tucson, Arizona, United States
- Janda, Jaroslav, The University of Arizona College of Pharmacy, Tucson, Arizona, United States
- Thompson, Austin D., The University of Arizona College of Pharmacy, Tucson, Arizona, United States
- Schnellmann, Rick G., The University of Arizona College of Pharmacy, Tucson, Arizona, United States
Group or Team Name
- Schnellmann Lab.
Background
Renal fibrosis is a debilitating hallmark of renal aging, which impairs both the structural and functional integrity of the kidney. Mitochondrial dysfunction has previously been shown to play a critical role in facilitating the onset/progression of fibrosis. Conversely, mitochondrial biogenesis (MB), the generation of new and functional mitochondria, may provide an effective strategy for combating renal fibrosis.
MARY1 is a novel experimental therapeutic that induces mitochondrial biogenesis (MB), restores renal function, and reduces renal fibrosis in a mouse model of acute kidney injury (AKI). We hypothesized that treatment with MARY1 would also decrease age-related renal fibrosis.
Methods
Mice were divided into four groups and treated daily for 3 weeks: 1) young (12-week-old) mice + vehicle [saline + 0.1% DMSO], 2) young mice + MARY1 [0.3 mg/kg] 3) aged (24-month-old) mice + vehicle, and 3) aged mice + MARY1 (n=8-10/group). Following treatment, kidneys were harvested, and cortical tissue was analyzed via immunoblotting and histological staining analysis.
Results
Masson’s Trichrome histological staining revealed increased renal fibrosis in aged versus young mice. Aged mice treated with MARY1 displayed reduced renal fibrosis compared to those treated with vehicle, young mice displayed the minimal staining. Immunoblot analysis revealed increased collagen-1 in aged mice and MARY1 treatment of aged mice reduced protein expression of collagen-1 by 43%. Additionally, alpha-smooth muscle actin (αSMA), a fibrotic marker, exhibited a 39% reduction in protein expression in MARY1 treated aged mice compared to aged vehicle controls.
Additionally, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), a glycolysis inducer, which has been shown to promote renal fibrosis, decreased 54% in the renal cortices of aged mice treated with MARY1, closely mirroring levels observed in young mice.
Conclusion
These results suggest a therapeutic potential of MARY1 in ameliorating age-related renal fibrosis. In addition, MARY1 may block the expression of PFKFB3.
Funding
- Veterans Affairs Support