Kidney Week

Abstract: FR-PO0374

Tubule-Specific Deletion of Cyclin G1 Attenuates Maladaptive Repair and Tubular Dedifferentiation in a Repeat Low-Dose Cisplatin AKI-to-CKD Model

Session Information

• AKI: Mechanisms - Metabolism and Repair
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Moriyama, Tomofumi, Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Tomofumi Moriyama, MD, PhD

• Takenaka, Yuto, Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Yuto Takenaka, MD, PhD

• Sugahara, Sho, Division of Diabetology, Endocrinology, and Nephrology, Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan

Sho Sugahara, MD, PhD

• Thompson, Freddiemae La'faith, Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Freddiemae La'faith Thompson

• Taguchi, Kensei, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan

Kensei Taguchi, MD, PhD, FASN

• Brooks, Craig R., Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Craig R. Brooks, PhD

Background

Acute kidney injury (AKI) is a significant clinical complication that predisposes patients to the development of chronic kidney disease (CKD) through maladaptive repair during the AKI-to-CKD transition. This transition is primarily driven by injured proximal tubule cells (PTCs) that fail to recover and remain in a maladaptive dedifferentiated state characterized by the expression of Sox9 and other injury-associated markers. Recent studies have highlighted the importance of stress-response pathways in regulating tubular cell fate during the AKI-to-CKD transition. In this study, we investigated whether kidney tubule cell-specific deletion of Cyclin G1 suppresses maladaptive repair and tubular dedifferentiation.

Methods

AKI-to-CKD transition was induced in Cyclin G1 flox/flox (fl/fl) mice and tubule-specific Cyclin G1 knockout mice (Cyclin G1ΔSix2) by repeat low-dose cisplatin administration (5 mg/kg weekly for 4 weeks). Renal function was assessed by blood urea nitrogen (BUN). Tubular injury, dedifferentiation, tubular integrity, and mitochondrial-associated markers were evaluated by immunofluorescence staining and RT-qPCR. Histological analyses were performed to assess tubular structural changes following injury.

Results

Following repeat low-dose cisplatin administration, CyclinG1fl/fl mice developed significant renal dysfunction with marked elevation of BUN levels, severe tubular injury, and disruption of tubular architecture. These changes were accompanied by increased expression of injury- and dedifferentiation-associated markers, including Kim1, Sox9, Vimentin, and VCAM1. In contrast, CyclinG1ΔSix2 mice demonstrated significantly attenuated BUN elevation, preservation of tubular structure, and suppression of injury and dedifferentiation marker expression. In addition, mitochondrial-associated markers were better
preserved in CyclinG1-deficient tubules, suggesting improved maintenance of tubular cellular homeostasis following injury.

Conclusion

These results suggest that tubular Cyclin G1 contributes to maladaptive repair and tubular dedifferentiation during the AKI-to-CKD transition. Targeting Cyclin G1-associated stress-response pathways may represent a potential therapeutic strategy for preventing CKD progression following recurrent tubular injury.

Funding

• NIDDK Support