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Kidney Week

Abstract: FR-PO130

Renal Injury Response in an Adult Pkd2 Mouse Model

Session Information

  • AKI: Mechanisms - II
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Cherakara, Sreelakshmi, The University of Alabama at Birmingham Department of Cell Developmental and Integrative Biology, Birmingham, Alabama, United States
  • Li, Zhang, The University of Alabama at Birmingham Department of Cell Developmental and Integrative Biology, Birmingham, Alabama, United States
  • Haycraft, Courtney J., The University of Alabama at Birmingham Department of Cell Developmental and Integrative Biology, Birmingham, Alabama, United States
  • Croyle, Mandy J., The University of Alabama at Birmingham Department of Cell Developmental and Integrative Biology, Birmingham, Alabama, United States
  • Yoder, Bradley K., The University of Alabama at Birmingham Department of Cell Developmental and Integrative Biology, Birmingham, Alabama, United States
Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by dysfunction of the primary cilium on the renal tubule epithelium due to either loss of proteins localized on the cilium or loss of cilia structure. Mutations in Pkd1 or Pkd2, which encode PC1 and PC2, respectively, result in progressive cyst formation in mouse models of ADPKD. Previous studies have shown that renal injury accelerates cyst formation in these models suggesting the cilium/PKD1/PKD2 is involved in regulating injury and repair responses. Here we evaluate the role of Pkd2 in regulating renal injury and repair processes and how dysregulation of this process may contribute to renal cyst formation.

Methods

The renal injury will be induced by a single IP injection of cisplatin (9.0 mg/kg body weight), a chemotherapeutic drug with nephrotoxic side effects in adult induced CAGG-CreERT2; Pkd2 mutant mice. We analyzed the percentage of SOX9 (an indicator of injury) expressing cells at 3-, 7-, 14-, 21-, 28-, and 35-days post cisplatin injury using immunofluorescence (IF) and FACS.

Results

The number of cells expressing SOX9 peaked 7 days after cisplatin injection in both Pkd2 mutants and wildtype controls then decreased through 28 days post injury. In wild type controls, a small number of SOX9+ cells remained at 28- and 35-days post injury. However, in Pkd2 mutants, the number of cells expressing SOX9 at 28- and 35- days were more in injured epithelial cells than in the controls. In Pkd2 mutant kidneys, many of the epithelial cells lining the forming cysts continue to express SOX9, and this number increases during cyst expansion.

Conclusion

These data show that following renal injury, Pkd2 mutant and control kidneys have a similar increase in SOX9 expression in response to cisplatin-induced injury. However, in Pkd2 mutant mice, the number of SOX9+ cells at 28-days post-cisplatin is higher when compared to controls and begins to increase through day 35. This suggests that the Pkd2 mutant epithelium cannot complete the repair process after injury and Pkd2 might be required for the completion of the repair process.

Funding

  • NIDDK Support