# Epigenetic Regulation of Kidney Fibrosis following AKI

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $409,354

## Abstract

SUMMARY
Episodes of acute kidney injury (AKI) are associated with an increased risk for chronic kidney
disease (CKD); a permanent loss of kidney function. Following AKI, crosstalk between epithelial
and interstitial cells is critical for kidney healing (adaptive response) but if prolonged fosters CKD
(maladaptive). Evidence suggests that epigenetic modifiers, such as histone deacetylases
(HDACs) and microRNAs (miRs), can become deranged leading to pathological conditions. For
example, activation of kidney HDACs following AKI is hypothesized to exacerbate injury; however,
we and others have demonstrated that HDACs are also necessary for epithelial repair. A gap in
our knowledge exists in the kidney cell type specific, HDAC isoform-dependent mechanisms of
repair or chronic injury in response to AKI. We identified that following AKI, HDAC1 is significantly
increased in the kidney cortex including in fibroblasts and pericytes. Utilizing inducible, fibroblast-
specific HDAC1 knockout (KO) mice, we found that fibroblast/pericyte HDAC1 results in
myofibroblast activation and fibrosis. One potential target of HDAC1 may be miR-215-5p
(miR215). miR215 is reduced by in vivo HDAC inhibition, and is increased by HDAC1 in kidney
fibroblast/pericyte cells. We provide data that fibroblast miR215 is profibrotic. From these data,
we propose to test the following hypotheses: Aim 1: To test the hypothesis that AKI-mediated
fibrosis is dependent on activation of fibroblast/pericyte cell HDAC1. Aim 2: To test the
hypothesis that AKI promotes miR215 dependent interstitial fibrosis in the kidney. The
experiments proposed in this R01 will provide deep molecular evidence of epigenetic regulation
of the kidney fibroblast/pericytes following AKI and we will determine the dynamic epigenetic
patterning during CKD transition. Using both biased and unbiased approaches will result in the
identification of novel pathways that likely be of therapeutic value to help attenuate AKI-CKD
transition.

## Key facts

- **NIH application ID:** 10810713
- **Project number:** 5R01DK126664-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Kelly Hyndman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $409,354
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810713

## Citation

> US National Institutes of Health, RePORTER application 10810713, Epigenetic Regulation of Kidney Fibrosis following AKI (5R01DK126664-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10810713. Licensed CC0.

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