# Targeting histone deacetylase 3 for chronic kidney disease

> **NIH VA I01** · VA CONNECTICUT HEALTHCARE SYSTEM · 2022 · —

## Abstract

PROJECT SUMMARY
 Chronic kidney disease (CKD) is a public health problem that affects more than 26 million Americans.
The prevalence of CKD in the veteran population is 34% higher than in the general US population. A key
pathologic feature of CKD is renal inflammation resulting in initiation and progression of chronic kidney disease
to end-stage kidney disease. The current therapeutic options for this progressive condition are limited and often
ineffective. Therefore, a better understanding of the molecular mechanisms underlying renal inflammation is
essential for developing effective strategies for the treatment of CKD.
 We have studied the factors initiating and controlling renal inflammation and have discovered a critical
role of histone deacetylase 3 (HDAC3) in the regulation of renal inflammation during the development of CKD.
Our preliminary studies have demonstrated that the activation of macrophages and the production of
proinflammatory cytokines are dependent upon induction of HDAC3 in the kidney. Genetic deletion or
pharmacological inhibition of HDAC3 prevents macrophage activation and proinflammatory molecule production.
Furthermore, the proinflammatory effect of HDAC3 appears to be mediated by regulating nuclear factor kappa
B (NF-kB) signaling pathway. In this application, we plan to examine and characterize the role of HDAC3 in
macrophage activation and proinflammatory molecule production to further understand the cellular and molecular
mechanisms of renal inflammation. Our central hypothesis is that HDAC3 deacetylates histones resulting in
chromatin remodeling, which allows NF-kB to access its DNA response elements to induce proinflammatory
molecule expression. To test our hypothesis, we will pursue the following Specific Aims: Specific Aim 1 is to
determine the role of HDAC3 in the macrophage activation and proinflammatory molecule production; Specific
Aim 2 is to explore the molecular mechanisms by which HDAC3 promotes macrophage activation and
proinflammatory molecule production; and Specific Aim 3 is to evaluate the therapeutic potential of a selective
HDAC3 inhibitor for CKD.
 In summary, we plan to utilize molecular, cellular, pharmacological, and genetic approaches to study the
role of HDAC3 in macrophage activation and development of renal injury. Results from our studies will provide
a new understanding of the cellular and molecular mechanisms of renal inflammation and could lead to the
development of novel therapeutic strategies for the treatment of CKD.

## Key facts

- **NIH application ID:** 10293595
- **Project number:** 5I01BX002650-06
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** YANLIN WANG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2015-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293595

## Citation

> US National Institutes of Health, RePORTER application 10293595, Targeting histone deacetylase 3 for chronic kidney disease (5I01BX002650-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10293595. Licensed CC0.

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