# HDAC6 regulation of ICAM-1 expression and endothelial inflammatory signaling in sepsis

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $382,500

## Abstract

Project Summary
Sepsis is a life-threatening disease with high morbidity and mortality. New therapeutic strategies
are urgently needed to treat this devastating disease. Uncontrolled endothelial inflammatory
responses, which often leads to inflammatory vascular injury, contribute to the pathogenesis of
multiple organ failure in sepsis. HDAC6, a histone deacetylase, has been reported to modulate
nuclear and non-nuclear protein function through deacetylation. In this project, we will
investigate HDAC6 regulation of endothelial inflammatory injury during sepsis. In our preliminary
studies, we demonstrated that HDAC6 knockdown or selective HDAC6 inhibition prevented
TNF-α induced endothelial ICAM-1 expression, which was associated with increased α-tubulin
acetylation and reduced STAT1 activation. Furthermore, in mouse models of sepsis, HDAC6
inhibition blocked sepsis-induced lung ICAM-1 expression, induced α-tubulin acetylation, and
suppressed STAT1 activation in lung tissues, which was associated with reduced lung
inflammatory injury and increased survival rate. In the proposed studies, we will conduct a serial
of experiments to assess the role of HDAC6 in sepsis-induced endothelial inflammatory
responses, and to investigate therapeutic mechanisms of HDAC6 inhibition against endothelial
inflammatory signaling in sepsis.

## Key facts

- **NIH application ID:** 9923729
- **Project number:** 5R01HL137910-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Jian Fu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2018-06-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923729

## Citation

> US National Institutes of Health, RePORTER application 9923729, HDAC6 regulation of ICAM-1 expression and endothelial inflammatory signaling in sepsis (5R01HL137910-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9923729. Licensed CC0.

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