Daniel Batlle, MD, the Earle, del Greco, Levin Professor of Nephrology/Hypertension, was a co-author of the study published in Cell.
Scientists have discovered previously unknown cellular mechanisms that regulate the production of renin, an essential enzyme in the kidney, findings that could improve the understanding of how the kidney regulates its function and how chronic kidney disease develops, according to a recent study published in Cell.
Daniel Batlle, MD, the Earle, del Greco, Levin Professor of Nephrology/Hypertension in the Department of Medicine, was a co-author of the study.
Renin is an enzyme that is synthesized and secreted by the kidney to help control blood pressure and also works with angiotensin II and aldosterone hormones to maintain levels of sodium and potassium throughout the body.
Renin production stems from juxtaglomerular granular (JG) cells in the kidney and plays a key role in the renin-angiotensin-aldosterone system (RAAS) which regulates blood pressure and volume status.
One of the mechanisms that stimulates renin release is a decrease in blood flow in the kidneys, suggesting a link between this “mechanosensation” and renin production, according to the authors, but has remained poorly understood up until now.
Using a combination of techniques including in vivo calcium imaging to study mice and human kidney tissue samples, a group of scientists from several institutions led by Rose Hill, PhD, and Ardem Patapoutia, PhD, from Scripps Research Institute, found that the kidney uses a mechanical sensing mechanism through the PIEZO2 ion channel that allows JG cells to directly sense changes in blood flow and pressure.
PIEZO2 is a mechanically gated ion channel protein that allows cells across organ systems to sense physical forces, such as stretch and pressure.
“PIEZO2 channels are usually involved in sensory nerve cells that detect light touch and body position changes whereas in this study it was shown that PIEZO2 regulates the release of renin via calcium signaling in renin-producing cells within the kidney” Batlle said.
In mice engineered with JG cells lacking PIEZO2, the scientists discovered that renin release was significantly increased and impacted downstream peptides and enzymes within the RAAS. They also found that PIEZO2 regulates renin during acute and chronic blood volume imbalances.
“If you eliminate PIEZO2 from renin-producing cells using a conditional knockout mouse model, renin goes sky high. It’s like you are liberating the break and then all of a sudden are releasing a lot of renin,” Batlle said.
The findings identify PIEZO2 as a key regulator of renin production and overall JG cell function, which could help improve the understanding of how the kidneys start overfiltering, such as seen in diabetes that later develops into chronic kidney disease, and other poorly understood kidney diseases, according to the authors.
This work was supported by the National Institutes of Health grants K99NS133478, K01DK121737, R01HL148044, R01DK132066, 5R01DK097598, R01DK128660, R01DK141178, R01DK064324 and S10OD021833; American Heart Association grant 20CDA35320169; the Collins Medical Trust; ASN KidneyCure; and a Howard Hughes Medical Institute Investigator Award.