Renin-Angiotensin System Signaling in Parietal Epithelial Cells

Abstract

INTRODUCTION. Bowman's capsule surrounds the kidney glomerular tuft and consists of a monolayer of parietal epithelial cells (PECs) creating a physiologically functioning barrier between the urinary space and the renal interstitium. Pathophysiological PEC activation describes the phenotypic switch from their normal quiescent state to one of proliferation and migration to the glomerular tuft, leading to glomerular injury. The development of several proteinuric kidney diseases is closely associated with PEC activation, however, the mechanisms of functional receptor signaling in these cells are not well described. This study investigates the functional presence of renin-angiotensin system (RAS) components and corresponding intracellular mechanisms in PECs. Methods. The vibrodissociation method was utilized to obtain freshly isolated Bowman’s capsules from discarded adult male human transplant tissues and 12-week old Wistar male and female rats. Confocal fluorescent microscopy of freshly isolated Bowman’s capsule PECs was performed using Fluo-8 or DAF-FM fluorescent dyes to detect changes in intracellular Ca2+ concentrations and nitric oxide (NO) response to the variety of RAS peptides. RESULTS. In separate experiments on freshly isolated rodent and human Bowman’s capsule PECs, we demonstrate the changes in redox response to the stimulation of RAS components. In particular, the acute application of Ang II peptide caused a rapid increase in NO production. Interestingly, we did not indicate significant changes in intracellular Ca2+ influx. To find out which receptor is responsible for the NO release we preincubated PECs with AT1R and AT2R blockers (Losartan and PD123319 respectively). Our data indicate that RAS mediates NO production through the AT2R activation. There is no sex difference was observed in these experiments. Further experiments with the variety of nitric oxide synthase (NOS) pharmacology reveal the functional distribution of NOS in rodent PECs. CONCLUSION. Our study provides an overview of the RAS signaling within PECs. For the first time, we present evidence demonstrating a direct connection between Ang II and redox homeostasis in PECs. Further investigation using the developed approach will be essential for understanding the role of Bowman's capsule cells in the glomerulus and the development of potential treatment against the hyperplasia of activated PECs and corresponding chronic kidney pathologies. Funding Sources: R01 DK129227, R01 DK126720, VA CDA-2 1IK2BX005605-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.