# Role of NOD2 in ischemia reperfusion injury

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $435,375

## Abstract

Project Summary: This proposal studies how a key cytoplasmic innate immune receptor, NOD2,
contributes to renal ischemia reperfusion (IR) injury. The project is highly significant for ischemic kidney
injury, as occurs frequently in hospitalized patients.
Broad/long-term objectives: The long-term goals of the proposed research are to define how NOD2
contributes to injurious tissue responses in the kidney.
Specific Aims: The specific objective of this proposal is to test the hypothesis that the cytoplasmic pattern
recognition receptor NOD2 is a key contributor to renal tubular epithelial damage induced by renal IR injury.
Aim 1 asks whether NOD2 activation directs renal tubular epithelial cell injury, defines the signaling events
that lead to this injury, and determines whether NOD2 blockade prevents renal tubular epithelial injury.
Aim 2 asks whether activation of NOD2 contributes to ischemic renal injury primarily through direct (local)
or indirect (systemic) mechanisms.
Research Design and Methods for Achieving the Stated Goals: Aim 1 will test how ligation of NOD2
injures renal tubular epithelial cells, whether the NOD2 activating stimulus directs the mode of RTE cell
injury, how molecules released from necrotic cells (DAMPs) activate NOD2-mediated injury of healthy RTE
cells, and whether RTE cell injury can be blocked by either blocking NOD2 or one of its upstream activating
pathways. In vivo IR injury incorporates other mediators of tissue injury, such as inflammation, so aim 2
focus on whether NOD2 activation plays a broader role in the kidney by separating local (kidney injury) from
systemic (inflammation). Direct (local, kidney specific) effects are separated from indirect (systemic) effects
in a kidney transplant model where injury responses of the NOD2-/- transplanted kidney are studied in a wild
type (WT) host, and WT kidney injury studied in a NOD2-/- host.
Health Relatedness of Project: If the aims of this proposal are met we will learn how molecules released
from injured tissue activate NOD2-dependent injurious responses in the kidney. This knowledge is crucial for
the development of rational target therapies for prevention or amelioration of renal IR injury in clinical
situations where hypoxia is anticipated. Focusing on the earliest events of ischemic kidney injury holds the
greatest promise for effective therapeutic strategies.

## Key facts

- **NIH application ID:** 9970470
- **Project number:** 5R01DK113162-04
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Dianne B Mckay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $435,375
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970470

## Citation

> US National Institutes of Health, RePORTER application 9970470, Role of NOD2 in ischemia reperfusion injury (5R01DK113162-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9970470. Licensed CC0.

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