Kidney Week

Abstract: TH-PO0262

Apold1 Deficiency Impairs Glomerular Endothelial Regeneration and Exacerbates Inflammation After Kidney Injury

Session Information

• Glomerular Diseases: Cell Biology
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Seitz, Meike, Universitatsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik III, Dresden, SN, Germany

Meike Seitz, MS, MSc

• Sradnick, Jan, Universitatsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik III, Dresden, SN, Germany

Jan Sradnick, PhD

• Dubau, Lilly Sophie, Universitatsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik III, Dresden, SN, Germany

Lilly Sophie Dubau

• Hartmann, Pilar Elisa, Universitatsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik III, Dresden, SN, Germany

Pilar Elisa Hartmann

• Weissbach, Hannah, Universitatsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik III, Dresden, SN, Germany

Hannah Weissbach, MS

• Wirth, Anika, Universitatsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik III, Dresden, SN, Germany

Anika Wirth

• Todorov, Vladimir T., Universitat Witten/Herdecke, Witten, NRW, Germany

Vladimir T. Todorov, MD, PhD

• Hugo, Christian, Universitatsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik III, Dresden, SN, Germany

Christian Hugo, MD

Background

Recent research has demonstrated that endothelial cells (ECs) exhibit significant heterogeneity, displaying remarkable plasticity in both normal and pathophysiological conditions. However, the precise cellular responses of renal ECs during injury and regeneration remain poorly understood. Characterizing the regeneration of glomerular ECs (gECs) using single-cell RNA sequencing, we found the EC-specific gene Apold1 to be highly upregulated during the regenerative phase after glomerular endothelial specific injury. While Apold1 is a known regulator of angiogenesis in pathological settings, its function in the kidney is unknown. Thus, we utilized Apold1-deficient mice (Apold1 ^-/-) to characterize the gene's influence on gEC regeneration following gEC-specific injury.

Methods

gEC-specific injury was induced in Apold1^-/- and C57BL/6J (WT) mice via renal arterial perfusion with Concanavalin A (ConA)/anti-ConA serum. Sham-operated mice served as baseline controls for both genotypes. Kidneys were harvested 1 and 7 days post-injury. EC damage and regeneration were characterized using histological and immunohistological staining on zinc-fixed, paraffin-embedded sections, and analyzed with AQUISTO, a semi-automatic quantification software.

Results

PAS staining revealed comparable damage on day 1 post-injury. Staining for the EC marker Endomucin (EMCN) showed a significant reduction in EMCN-positive glomerular area on day 1 for both injured genotypes relative to healthy shams (Apold1 ^-/-: 34.8% vs sham 39.9% ; WT: 34.8% vs sham 39.7%). However, while WT EMCN-positive area returned to sham levels by day 7 (39.3%), Apold1 ^-/- mice exhibited impaired recovery (37.3%). Furthermore, by day 7, Apold1 ^-/- mice displayed aberrant glomerular endothelial morphology with EC dilation, accompanied by significantly higher immune cell infiltration (CD45+ cells) compared to WTs.

Conclusion

In conclusion, the absence of Apold1 leads to impaired glomerular endothelial regeneration and an increased inflammatory response following selective injury. Our findings demonstrate that Apold1 plays a central role in glomerular endothelial regeneration. We believe that Apold1-mediated angiogenesis represents a crucial mechanism and could serve as a potential therapeutic target for the treatment of kidney injury.

Funding

• Government Support – Non-U.S.