# Ischemic Kidney Injury and Kidney Repair: Stress Granules

> **NIH VA I01** · CHARLIE NORWOOD VA MEDICAL CENTER · 2023 · —

## Abstract

AKI is a major kidney disease that is associated with high mortality, morbidity, and increasing
prevalence. Moreover, incomplete or maladaptive kidney repair following AKI leads to chronic renal
pathologies, contributing to CKD. Aging population, mirrored by veterans, is highly susceptible to both
AKI and CKD. A key pathological feature of AKI is the damage of renal tubules and, accordingly, the
past research has focused on tubular cell injury and death. However, it is known that, in response to
injury, cells may activate intrinsic mechanisms or stress responses for self-protection and survival, and
the cells die only when these mechanisms are overwhelmed or altered by severe or prolonged insult.
Stress granule (SG) is a newly discovered, cytoplasmic structure formed in eukaryotic cells upon cell
stress, which mainly contains RNAs and RNA-binding proteins. We recently demonstrated the first
evidence of SG formation in stressed kidney tubular cells. We have now established the first mouse
model in which the core SG gene G3BP1 is specifically ablated from kidney proximal tubule cells. In
addition, we have identified CSDE1 as a novel binding protein of G3BP1. The goal of this application
is to determine the pathologic role of SG in ischemic AKI and maladaptive kidney repair, and elucidate
the molecular interaction between G3BP1 and CSDE1. We hypothesize that: Stress granules are
induced in ischemic AKI to protect kidney tubular cells, but persistent stress granules after AKI may
contribute to maladaptive repair. Through the interaction with G3BP1, CSDE1 plays an important role
in SG formation during cell stress in conditions like ischemic AKI. We propose three specific aims to:
(1) test the hypothesis that stress granules are induced in ischemic AKI to protect against renal tubular
damage; (2) test the hypothesis that stress granules contribute to maladaptive kidney repair after
ischemic AKI; and (3) test the hypothesis that CSDE1 plays an important role in stress granule
formation through the interaction with G3BP1. This application will unveil the role of stress granules in
AKI and post-AKI kidney repair, and elucidate G3BP1/CSDE1 interaction in stress granule formation.
As such, completion of the work will not only gain significant insights into the regulation of stress
granules, but may also identify stress granule as a novel therapeutic target for AKI and associated
CKD, opening a new field of study.

## Key facts

- **NIH application ID:** 10507755
- **Project number:** 5I01BX000319-14
- **Recipient organization:** CHARLIE NORWOOD VA MEDICAL CENTER
- **Principal Investigator:** Zheng Dong
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2009-04-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507755

## Citation

> US National Institutes of Health, RePORTER application 10507755, Ischemic Kidney Injury and Kidney Repair: Stress Granules (5I01BX000319-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10507755. Licensed CC0.

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