# Mechanisms and therapeutic manipulation of retinoic acid signaling in Acute Kidney Injury

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $426,720

## Abstract

Acute kidney injury (AKI) is a serious disorder that involves a rapid decline in renal function over a period of hours to
days. Severe cases can result in end-stage renal disease, and evidence suggests that AKI is a precursor to long-term
chronic renal disease (CKD). Despite this, there is no targeted clinical treatment for AKI. Specifically, no therapies exist
that accelerate renal recovery or decrease fibrosis and CKD when administered after injury. However, the kidney
possesses an inherent capacity to repair after AKI, and a promising approach to ameliorate long-term AKI-mediated
damage lies in developing novel therapies that can enhance the natural mechanisms of tissue repair in order to reduce
fibrosis and CKD after AKI. Macrophages play a central role in coordinating the injury and repair process after AKI, but
the intrinsic mechanisms control macrophage-dependent repair after AKI have been poorly understood. In recent studies
we have shown that retinoic acid (RA) signaling plays an important role in regulating this macrophage-dependent repair
and fibrosis after AKI and that therapeutic manipulation of this pathway might be used to safely manipulate this RA-
dependent response for therapeutic benefit for AKI. In this proposal we plan a series of mouse and cell culture studies to
explore the mechanisms by which RA signaling regulates this response, and to develop a novel pre-clinical therapeutic
platform to safely and effectively enhance local activation of the RA signaling pathway in the kidney in order to increase
macrophage-dependent tissue repair and reduce the likelihood of developing long-term CKD after an episode of AKI.

## Key facts

- **NIH application ID:** 9924588
- **Project number:** 5R01DK112688-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Mark P. de Caestecker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $426,720
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924588

## Citation

> US National Institutes of Health, RePORTER application 9924588, Mechanisms and therapeutic manipulation of retinoic acid signaling in Acute Kidney Injury (5R01DK112688-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9924588. Licensed CC0.

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