Kidney Week

Abstract: TH-PO0383

Clinically Relevant Polo-Like Kinase Inhibitors to Preserve Podocyte Structural Integrity During Injury

Session Information

• Glomerular Diseases: Genetics to Therapeutics
  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

• Machineni, Prathyushasai, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States

Prathyushasai Machineni, MS

• Tefera, Mahilet A., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States

Mahilet A. Tefera

• Youssef, Mohamed A., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States

Mohamed A. Youssef, MD

• Akmal, Maarya, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States

Maarya Akmal, MD

• Helmuth, Richard, Rush University Medical Center, Chicago, Illinois, United States

Richard Helmuth, MS

• Lee, Ha Won, Rush University Medical Center, Chicago, Illinois, United States

Ha Won Lee, PhD

• Han, Zhe, University of Maryland Baltimore, Baltimore, Maryland, United States

Zhe Han, PhD

• Knott, Brenna, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States

Brenna Knott, MA, MBA

• Gupta, Vineet, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States

Vineet Gupta, PhD, FASN

Background

Focal segmental glomerulosclerosis (FSGS) remains a devastating condition with a critical unmet need for therapies that directly target podocyte preservation. Podocyte structural failure is central to glomerular filtration barrier dysfunction and disease progression. Polo-like kinase 2 (PLK2), a stress-activated serine/threonine kinase, is an emerging mediator of injury-associated cytoskeletal remodeling in podocytes. Critically, small-molecule PLK inhibitors already exist, positioning this pathway as an actionable drug repurposing opportunity. We hypothesized that pharmacologic inhibition of PLK-associated signaling could preserve podocyte structural integrity during injury.

Methods

Conditionally immortalized mouse podocytes were subjected to puromycin aminonucleoside (PAN) induced injury and treated with small-molecule PLK inhibitors. Podocyte morphology, actin cytoskeletal organization, focal adhesion integrity, and nucleocytoskeletal architecture were evaluated using high-content immunofluorescence imaging and quantitative image analysis. Cell viability and compound-associated cytotoxicity were assessed via nuclei counts and injury-independent morphology metrics.

Results

PAN injury induced marked cytoskeletal disorganization, podocyte morphological deformation, and focal adhesion disruption. Pharmacologic PLK inhibition potently reversed these injury-associated structural abnormalities, restoring actin organization, focal adhesion integrity, and nucleocytoskeletal architecture compared to injured controls. These findings implicate a PLK2 nucleoporin signaling axis as a novel driver of podocyte structural collapse and identify it as a tractable therapeutic target.

Conclusion

Clinically relevant PLK inhibitors—with established pharmacologic profiles—preserve podocyte structural organization following injury in vitro, providing a compelling rationale for their repurposing in FSGS. These findings open a rapid translational path toward podocyte-targeted therapies and warrant further investigation in preclinical models of glomerular disease.