Kidney Week

Abstract: FR-PO783

Unveiling Functional Renin-Angiotensin System-Related Signaling in Parietal Epithelial Cells

Session Information

• Glomerular Diseases: Mechanisms and Podocyte Biology
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Fedoriuk, Mykhailo, Medical University of South Carolina, Charleston, South Carolina, United States

Mykhailo Fedoriuk, MS, MSc, PhD

• Stefanenko, Mariia, Medical University of South Carolina, Charleston, South Carolina, United States

Mariia Stefanenko, MS, MSc

• Van Beusecum, Justin Pieter, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States

Justin Pieter Van Beusecum, PhD

• Ilatovskaya, Daria, Augusta University, Augusta, Georgia, United States

Daria Ilatovskaya, MS, PhD

• Palygin, Oleg, Medical University of South Carolina, Charleston, South Carolina, United States

Oleg Palygin, PhD

Background

The Bowman's capsule envelops the kidney's glomerular tuft, comprised of a single layer of parietal epithelial cells (PECs) that form a vital barrier between the urinary space and the renal interstitium. When PECs undergo pathophysiological activation, they transition from their usual quiescent state to one characterized by proliferation and migration towards the glomerular tuft, causing glomerular injury. Numerous proteinuric kidney diseases are linked to PEC activation, yet the precise mechanisms governing functional receptor signaling in these cells remain poorly understood. This study aims to explore the presence of components of the renin-angiotensin system (RAS) and the corresponding intracellular mechanisms within PECs.

Methods

The vibrodissociation technique was utilized to obtain freshly isolated Bowman’s capsules with PECs from discarded adult male human transplant tissues and 12-week-old Wistar male and female rats. Live confocal microscopy detected changes in intracellular Ca²⁺ concentrations (Fluo8) and nitric oxide (NO; DAF-FM) response to acute Ang II applications. Scanning electron microscopy (SEM) was used to examine the PECs structure.

Results

In SEM, we confirmed the intact nature of the isolated PECs of the Bowman capsule. The acute administration of Ang II peptide elicited rapid NO production in cells isolated from both males and females, while no significant intracellular Ca²⁺ influx in response to Ang II. To identify the functional receptor responsible for Ang II signaling in PECs, we preincubated cells with AT1R or AT2R blockers (Losartan and PD123319, respectively). Our findings demonstrated that Ang II facilitates NO production via AT2R activation, which held true in both sexes. Importantly, in separate experiments, we confirmed the similarity of these signaling mechanisms between the rat and human species.

Conclusion

Our research offers insight into Ang II-mediated signaling within PECs. For the first time, we present evidence establishing a direct link between Ang II and redox homeostasis in PECs. Further exploration utilizing this newly developed approach will be crucial for understanding the involvement of PECs in glomerular function and devising potential treatments targeting the hyperplasia of activated PECs and associated chronic kidney pathologies.

Funding

• NIDDK Support