Renal PIEZO2 is an essential regulator of renin
Renin synthesis and release is the rate-limiting step of the renin-angiotensin-aldosterone system (RAAS) that controls fluid homeostasis. A major activator of the RAAS is a decrease in perfusion pressure within the kidneys, suggesting a link between renal mechanotransduction and renin. However, the identity of the mechanosensor(s) in the kidneys and their physiological significance to the RAAS remain unclear. We find that loss of the force-gated nonselective cation channel PIEZO2 in cells of renin lineage dysregulates the RAAS by elevating renin. We observe that PIEZO2 is expressed in renin-producing juxtaglomerular granular cells and is required for their calcium dynamics in vivo. PIEZO2 deficiency in cells of renin lineage drives renin-dependent and MAS-receptor-dependent glomerular hyperfiltration and regulates the RAAS during acute and chronic blood volume challenges. Collectively, our study identifies PIEZO2 as an essential regulator of juxtaglomerular granular cell calcium activity and renin in vivo.
Authors
- James A. McCormick (ORCID: https://orcid.org/0000-0003-4000-6653)
- Daniel Batlle (ORCID: https://orcid.org/0000-0002-5878-9046)
- János Peti‐Peterdi (ORCID: https://orcid.org/0000-0003-4092-6185)
- Jan Wysocki (ORCID: https://orcid.org/0000-0002-8429-272X)
- Adrienne E. Dubin (ORCID: https://orcid.org/0000-0003-4683-7175)
- R. Ariel Gómez (ORCID: https://orcid.org/0000-0002-5124-8255)
- Abirami Lakshmanan
- Jonathan W. Nelson (ORCID: https://orcid.org/0000-0003-1456-9399)
- Silvia Medrano (ORCID: https://orcid.org/0000-0002-8516-0788)
- J. Ahmed
- Georgina Gyarmati (ORCID: https://orcid.org/0000-0003-3452-7970)
- Stuart J. Shankland (ORCID: https://orcid.org/0000-0002-4616-8330)
- Rose Z. Hill (ORCID: https://orcid.org/0000-0001-9558-6400)
- Ardem Patapoutian
- Maria Luisa S. Sequeira-Lόpez (ORCID: https://orcid.org/0000-0002-4459-7940)
- Diana G. Eng (ORCID: https://orcid.org/0000-0003-1157-917X)
- Sepenta Shirvan
- Sebastian Burquez
- Jeffrey H. Miner (ORCID: https://orcid.org/0000-0002-1510-8714)
- M Rocio Servin-Vences
Institutions
- Northwestern University (US)
- University of Southern California (US)
- Scripps Research Institute (US)
- Howard Hughes Medical Institute (US)
- Oregon Health & Science University (US)
- University of Washington (US)
- Washington University in St. Louis (US)
- University of Virginia (US)
Publication Details
- Journal
- Cell
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1016/j.cell.2025.11.013
- Citations
- 3
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 3.49