Kidney Week

Abstract: FR-PO157

DNA-Binding Protein-A Promotes Kidney Ischemia-Reperfusion Injury and Participates in Mitochondrial Function

Session Information

• AKI: Mechanisms
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Reichardt, Charlotte, Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Sachsen-Anhalt, Germany

Charlotte Reichardt, MS, MSc

• Brandt, Sabine, Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Sachsen-Anhalt, Germany

Sabine Brandt

• Krause, Anna, Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Sachsen-Anhalt, Germany

Anna Krause

• Lindquist, Jonathan A., Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Sachsen-Anhalt, Germany

Jonathan A. Lindquist, PhD

• Geffers, Robert, Helmholtz-Zentrum fur Infektionsforschung GmbH, Braunschweig, Niedersachsen, Germany

Robert Geffers

• Franz, Tobias, Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Sachsen-Anhalt, Germany

Tobias Franz, MD

• Kahlfuß, Sascha, Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Sachsen-Anhalt, Germany

Sascha Kahlfuß

• Mathew, Akash, Universitat Leipzig, Leipzig, Sachsen, Germany

Akash Mathew, MSc

• Rana, Rajiv, Universitat Leipzig, Leipzig, Sachsen, Germany

Rajiv Rana, MSc

• Mertens, Peter R., Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Sachsen-Anhalt, Germany

Peter R. Mertens, MD, DrMed

Background

DNA binding protein A (DbpA), encoded by the Ybx3 gene, is a member of the cold shock protein family and is involved in cell cycling, transcription, translation, and tight junction communication. While DbpA is known to be upregulated in chronic nephritis, its functions in acute injury models, such as renal ischemia/reperfusion injury (IRI), remain unclear.

Methods

Mice with Ybx3^+/+, Ybx3^+/-, or Ybx3^-/- genotypes were characterized over a period of 24 months and following experimental renal IRI. Metabolic processes such as mitochondrial function, number and integrity were analyzed by mito/glycolysis stress tests, MitoTracker staining, Western blotting and electron microscopy. Additionally, RNA sequencing, immunohistochemistry, Western blotting, and flow cytometry were performed to measure tubular cell damage, tissue scarring, and immune cell infiltration.

Results

DbpA is dispensable for kidney development and tissue homeostasis under healthy conditions. Notably, the endogenous DbpA protein is localized within the mitochondria of primary tubular epithelial cells (TECs). However, genetic deletion of Ybx3 leads to notable changes in TECs, including increased mitochondrial membrane potential, enhanced lipid uptake and metabolism, elevated oxygen consumption rates (OCR), and glycolytic activities.
In mice lacking Ybx3, protection against IRI is observed, characterized by reduced immune cell infiltration, diminished endoplasmic reticulum (ER) stress, less tubular cell damage, and decreased fibrosis. A putative protective mechanism is identified via upregulated antioxidant activities and reduced ferroptosis, when Ybx3 is deleted.

Conclusion

Here, experimental evidence shows that DbpA acts as a mitochondrial protein and has significant negative effects on cell metabolism. Moreover, the genetic deletion of Ybx3 reveals a protective effect against IRI.