# Dual Oxidase 2 as a New Target for Treatment of Diabetic Nephropathy

> **NIH NIH SC2** · UNIVERSITY OF THE INCARNATE WORD · 2024 · $135,541

## Abstract

Project Summary/Abstract
Glomerular epithelial cell/podocyte injury is a prominent pathological feature of diabetic nephropathy
(DN). In podocytes, hyperglycemia causes alteration of slit diaphragm proteins, foot process
effacement, apoptosis and cell detachment, events that ultimately results in loss of renal function. High
glucose concentrations (HG) and oxidative stress are potential mediators of glomerular injury in
diabetes. We have evidence that Dual oxidase 2 (Duox2) is expressed in glomerular cells and
contributes to HG-induced reactive oxygen species (ROS) generation as well as podocyte injury.
Additionally, we have demonstrated that glomeruli isolated from DuoxA-/- mice were protected from
high glucose-induced hydrogen peroxide generation. The central hypothesis of this proposal is that the
ROS generated by Duox2 play a pivotal role in glomerular lesions and podocyte injury in the diabetic
kidney. The goals of this proposal are to utilize in vitro and in vivo approaches to establish the
importance of Duox2 in podocyte injury in the diabetic environment and identify the factors that are
modulating Duox2 activity/expression. The role of Duox activators (DuoxA), translational mechanisms,
and calcium in Duox2 activation will be explored. For the in vivo studies, we will utilize previously
collected kidney cortices from diabetic and non-diabetic mice where DuoxA function is impaired. As no
data related to Duox enzyme expression and function within podocytes are available, the experiments
proposed should serve as proof of concept to demonstrate the utility of targeting the Duox/DuoxA
system to reduce diabetes-mediated glomerular lesions. Characterization of the deleterious actions of
Duox2 and identification of its regulators will contribute to the design of novel therapeutic interventions
and will help establish adjunct therapy to treat DN. The studies will stress the relevance of the
development of modulators of Duox2 expression and activity in the kidney as therapeutic agents to
prevent or reverse DN. Furthermore, this proposal will enhance the research and educational
infrastructure at the University of the Incarnate Word, introducing biomedical research experiences to
underrepresented minority students who would otherwise lack such opportunities.

## Key facts

- **NIH application ID:** 10866356
- **Project number:** 5SC2GM136569-03
- **Recipient organization:** UNIVERSITY OF THE INCARNATE WORD
- **Principal Investigator:** Bridget M Ford
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $135,541
- **Award type:** 5
- **Project period:** 2022-05-19 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866356

## Citation

> US National Institutes of Health, RePORTER application 10866356, Dual Oxidase 2 as a New Target for Treatment of Diabetic Nephropathy (5SC2GM136569-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10866356. Licensed CC0.

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