Porter, Aidan and Vorndran, Hannah and Marciszyn, Allison and Mutchler, Stephanie and Subramanya, Arohan and Kleyman, Thomas and Hendershot, Linda and Brodsky, Jeffrey and Buck, Teresa
(2025)
Dataset for Excess dietary sodium restores electrolyte and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.
[Dataset]
Abstract
The maintenance of fluid and electrolyte homeostasis by the kidney requires proper folding and trafficking of ion channels and transporters in kidney epithelia. Each of these processes requires a specific subset of a diverse class of proteins termed molecular chaperones. One such chaperone is GRP170, which is an Hsp70-like, endoplasmic reticulum (ER)-localized chaperone that plays roles in protein quality control and protein folding in the ER. We previously determined that loss of GRP170 in the mouse nephron leads to hypovolemia, electrolyte imbalance, and rapid weight loss. In addition, GRP170-deficient mice develop an acute kidney injury (AKI)-like phenotype, typified by tubular injury, elevation of kidney injury markers, and induction of the unfolded protein response (UPR). By using an inducible GRP170 knockout cellular model, we confirmed that GRP170 depletion induces the UPR, triggers apoptosis, and disrupts protein homeostasis. Based on these data, we hypothesized that UPR induction underlies hyponatremia and volume depletion in these rodents and that these and other phenotypes might be rectified by sodium supplementation. To test this hypothesis, control and GRP170 tubule-specific knockout mice were provided a diet containing 8% sodium chloride. We discovered that sodium supplementation improved electrolyte imbalance and kidney injury markers in a sex-specific manner but was unable to restore weight or tubule integrity. These results are consistent with UPR induction contributing to the kidney injury phenotype in the nephron-specific GR170 knockout model and indicate that GRP170 function in kidney epithelia is essential to both maintain electrolyte balance and ER homeostasis.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
Dataset
|
| Status: |
Published |
| Creators/Authors: |
|
| Date: |
February 2025 |
| Date Type: |
Publication |
| Publisher: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Pediatrics |
| Refereed: |
No |
| Related URLs: |
|
| Media of Output: |
Dataset |
| Type of Data: |
Text |
| Copyright Holders: |
Authors |
| Date Deposited: |
08 Apr 2025 18:12 |
| Last Modified: |
10 Apr 2025 15:50 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/48518 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[img]](https://d-scholarship.pitt.edu/style/images/fileicons/text_plain.png)
![[img]](https://d-scholarship.pitt.edu/style/images/fileicons/application_zip.png)
![[feed]](/images/feed-icon-32x32.png){kind=icon}