Importance of Molecular Chaperone GRP170 in Acute Kidney Injury
June 1, 2022
New research published in the journal JCI Insights has shown that the glucose-regulated protein 170 (GRP170) a molecular chaperone that functions to regulate protein folding in the endoplasmic reticulum (ER), can protect the cells of the nephron from stress and acute kidney injury.
Aidan W. Porter, MD, in the Division of Pediatric Nephrology at UPMC Children's Hospital of Pittsburgh, was the study's lead author.
Prior work by Dr. Porter and his research colleagues in the Brodsky Laboratory and the Center for Protein Conformational Disease at the University of Pittsburgh identified a connection between the unfolded protein response and ER stress in acute kidney injury. They also discovered GRP170’s role in maintaining normal levels of sodium and water through its regulation of the epithelial sodium channel.
In the new study, Dr. Porter and his colleagues further explored the role of GRP170 in a knockout mouse model and uncovered several new findings of the function of GRP170 in the kidney, especially its role in protecting against AKI. By more fully understanding how GRP170 functions to maintain ER protein homeostasis in the cells of the kidney, the research may lead to the identification of therapeutic targets to prevent or treat AKI.
Summary of Key Findings
Loss of GRP170 in the mouse kidney compromised kidney function and led to profound kidney injury. The mice suffered from hypovolemia and a disturbance in sodium balance. Dr. Porter and his colleagues also found that deleting GRP170 disrupted electrolyte channel expression in the nephron. Additionally, mice lacking GRP-170 showed classic markers and histologic findings of acute kidney injury. In the models, AKI appeared to accrue first in the proximal tubule but ultimately progressed throughout the entire structure of the nephron, suggesting that the proximal tubule is more susceptible to initial injury. The authors linked these findings to sustained activation of the unfolded protein response (UPR) in kidney cells.
Dr. Porter and colleagues are continuing their study of GRP170 by exploring the mechanisms by which the endoplasmic reticulum stress response contribute to kidney injury and, at the same time, whether existing therapeutics that blunt UPR activation can mitigate the extent of kidney damage.
Read more about the study’s findings and methods using the link below.
Learn more about Dr. Porter and the Division of Pediatric Nephrology at UPMC Children’s Hospital of Pittsburgh.
Reference
Porter AW, Nguyen DN, Clayton DR, Ruiz WG, Mutchler SM, Ray EC, Marciszyn AL, Nkashama LJ, Subramanya AR, Gingras S, Kleyman TR, Apodaca G, Hendershot AR, Brodsky JL, Buck TM. The Molecular Chaperone GRP170 Protects Against ER Stress and Acute Kidney Injury in Mice. JCI Insight. 2022 Mar 8; 7(15): e151869.
