# Targeting oxidative stress-induced epigenetic reprogramming in fibrotic disease

> **NIH NIH R15** · TEXAS TECH UNIVERSITY · 2022 · $364,515

## Abstract

Project Summary of Parent funded R15 (1R15DK121362-01A1)
The goal of this proposed study is to evaluate whether oxidative stress-induced epigenetic changes
act as a driving factor for fibrosis in kidney. Multiple or repeated acute injuries to the kidney due to
chronic exposure to toxicants lead to the development of kidney fibrosis, an irreversible disease for
which there is no current treatment. Environmental toxicants are major risk factors for chronic kidney
diseases. The generation of oxidative stress is the most common property of environmental toxicants.
In addition to the exogenous sources of oxidative stress, the endogenous factors or basic
characteristics of renal patients such as advanced age, diabetes and renal hypertension can also
predispose the individuals to increasing levels of oxidative stress compared with the general
population. In addition to genetic changes, the epigenetic mechanisms play an important role in
transcriptional regulation of genes. However, the coordinated sequences of epigenetic alterations that
drive oxidative stress-induced kidney fibrosis during CKD remain unknown. Our preliminary data
revealed that persistent exposure to oxidative stress induces pEMT and induced pluripotent stem cell-
like (iPSCs) feature, that are known to be associated with fibrosis. Based on preliminary data we
hypothesize that “epigenetic reprogramming induced by pro-oxidant nephrotoxicants acts as a driver
of cellular remodeling of kidney tubular epithelial cells through partial EMT and stemness leading to
fibrogenesis”. To achieve the goal of this proposal, we will first Identify the temporal sequence and
global distribution of epigenetic alterations during oxidative stress-induced fibrosis in kidney tubular
epithelial cells using in vitro cell culture and in vivo animal models. Secondly, the role of epigenetic
reprogramming of target genes for iPSCs and pEMT characteristics acquired by kidney epithelial cells
and their impact on activation of fibroblast into ECM-producing myofibroblast will be determined.
Finally, to evaluate the clinical significance of epigenetic therapy in inhibition of kidney fibrosis, we will
evaluate whether reversal of epigenetic alterations in fibrotic kidney cells restores normal kidney
epithelial characteristics and functions using in vitro and in vivo models. Kidney fibrosis is a well-
established pathological stage in the development of CKD. This study will lead to a better
understanding of the epigenetics-based molecular mechanism for oxidative stress-induced fibrosis
during CKD. Identification of target molecules in kidney fibrosis will help to establish pharmacological
interventions that could prevent the progression from acute tissue damage to an irreversible stage of
fibrosis in the kidney and potentially in other target organs.

## Key facts

- **NIH application ID:** 10606293
- **Project number:** 3R15DK121362-01A1S1
- **Recipient organization:** TEXAS TECH UNIVERSITY
- **Principal Investigator:** Kamaleshwar P Singh
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $364,515
- **Award type:** 3
- **Project period:** 2021-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10606293

## Citation

> US National Institutes of Health, RePORTER application 10606293, Targeting oxidative stress-induced epigenetic reprogramming in fibrotic disease (3R15DK121362-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10606293. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*