# Treatment of kidney disease in diabetes

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2021 · $351,732

## Abstract

Diabetes continues to be the leading causes of kidney disease in the U.S. and around the world. The
pathogenesis of diabetic kidney disease remains poorly understood. Despite beneficial interventions
implemented in patients with diabetes that mitigate some of its negative effects, kidney disease still progresses
in most of these patients. Recent evidence indicates that impairments in mitochondrial dynamics and function
plays an important role in diabetic kidney disease and brings promise to treatment strategies for improving
mitochondrial function and the related pathways that may prevent or slow the progression of kidney disease. In
this proposal, we aim to determine the mechanisms and novel signaling mechanisms of SIRT3 and ERR-α in
the prevention and treatment of diabetic kidney disease, mitochondrial dysfunction, and podocyte injury.
In Specific Aim 1, we will determine how the mitochondrial sirtuin SIRT3 modulates diabetic kidney disease,
including by regulating mitochondrial function and dynamics, and activating novel signaling pathways
determined by quantitative phosphoproteomics and acetylomics. In male and female mice with i) podocyte
specific SIRT3 knockout, or ii) transgenic overexpression of SIRT3 in podocytes, or iii) treated with a SIRT3
agonist, or iv) in podocytes grown in culture following SIRT3 overexpression or SIRT3 agonist treatment we will
determine the effects on mitochondrial function and progression of kidney disease. We will also perform
quantitative phosphoproteomics and acetylomics to determine novel signaling pathways that will be further
explored for mechanistic studies related to SIRT3 action in the kidney.
In Specific Aim 2, we will determine how the nuclear receptor ERR-α modulates diabetic kidney disease,
including by regulating mitochondrial function and dynamics, and activating novel signaling pathways
determined by quantitative phosphoproteomics and acetylomics. In male and female mice with i) podocyte
specific ERR-α knockout, or ii) transgenic overexpression of ERR-α in podocytes, or iii) treated with a ERR-α
agonist, or iv) in podocytes grown in culture following ERR-α overexpression or ERR-α agonist we will
determine the effects on mitochondrial function and progression of kidney disease. We will also perform
quantitative phosphoproteomics and acetylomics to determine novel signaling pathways that will be further
explored for mechanistic studies related to ERR-α effects in the kidney.

## Key facts

- **NIH application ID:** 10133461
- **Project number:** 5R01DK116567-04
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** MOSHE LEVI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $351,732
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133461

## Citation

> US National Institutes of Health, RePORTER application 10133461, Treatment of kidney disease in diabetes (5R01DK116567-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133461. Licensed CC0.

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