Proliferation does not contribute to murine models of renin cell recruitment

Aim Renin cells are essential for regulation of blood pressure and fluid‐electrolyte homeostasis. During homeostatic threat, the number of renin cells in the kidney increases, a process termed as recruitment. It has been proposed that recruitment occurs by proliferation, yet no systematic studies have been performed. We sought to determine the extent to which proliferation contributes to the recruitment process. Methods Mice were subjected to recruitment before analysing the renin cells’ cell cycle. For acute threats, we subjected SV129 and C57Bl6 mice to a low sodium diet plus captopril. Tissue sections from treated mice were co‐stained for proliferation markers (Ki67, PCNA, pH3 and BrdU) and renin. Chronic recruitment was studied in deletion models of aldosterone synthase and angiotensinogen through co‐immunostaining and counting mitotic figures in periodic acid‐Schiff‐stained sections. Finally, RNA‐seq of renin cells isolated from recruited mice was performed to study mitotic signature. Results Mice subjected to low salt and captopril displayed increases in renin cell number (312 ± 40 in controls to 692 ± 85 in recruited animals, P<.0001), 10‐fold increases in renin mRNA and fourfold increases in circulating renin. Co‐staining these kidney sections for proliferation markers revealed negligible proliferation of renin cells (<2%), indistinguishable from control animals. Similarly, chronic models of recruitment—aldosterone synthase KO and angiotensinogen KO—had negligible proliferation. Additionally, the transcriptome of recruited renin cells revealed overall downregulation of mitotic pathways when compared to proliferative cell lines. Conclusion Acute and chronic physiological threats to homeostasis produced a distinct increase in renin‐synthesizing cells, but we found no evidence to suggest the involvement of proliferation.