# Role of miRNA-TLR7 signaling in platelet activation and dysfunction in sepsis

> **NIH NIH K08** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $155,150

## Abstract

Project Summary
Sepsis is a critical clinical condition that is caused by dysregulated host immune response to infection and
characterized by organ failure and high mortality. Sepsis is associated with marked inflammation and
hemostatic activation that often leads to widespread microvascular thrombus formation and global clotting
dysfunction, a complication termed sepsis-induced coagulopathy (SIC). Toll-like receptors (TLRs) are innate
immune receptors that respond to pathogen (PAMPs) or host-derived danger molecules (DAMPs) and drive
profound inflammation. We have established a murine model of SIC characterized by time-dependent
thrombocytopenia, procoagulant consumption, and global clotting dysfunction, and identified a critical role
for TLR7 (a receptor for single-stranded RNAs, e.g., HIV RNA or microRNA) in the pathogenesis of SIC
including thrombocytopenia, procoagulant (e.g., tissue factor, TF) production, and global clotting
dysfunction. Moreover, we have observed increased circulating plasma miRNAs (e.g., miR-146a-5p) and
extracellular vesicles (EVs, miRNA carrier) in sepsis, and a close correlation between the plasma RNA
levels and sepsis severity. Both miR-146a-5p and septic plasma EVs induce proinflammatory and
procoagulant response via a TLR7-dependent manner. Based on these data and the literature, we
hypothesize that miRNA→TLR7 signaling plays an important role in regulating platelet activity and contributes
to platelet dysfunction in SIC. To test this hypothesis, we propose the following three Specific Aims. In Aim
1, we will test the function and mechanisms of miRNA-TLR7 signaling in platelet activation. In Aim 2, we
will determine the effect of EVs loaded with miR-146a-5p and septic plasma EVs on platelet activation and
function. In Aim 3, we will investigate the role of TLR7 signaling in platelet activation and dysfunction in SIC.
Completion of the proposed studies will provide new insight into the role and mechanism of miRNA-TLR7
signaling in regulating platelet activity and dysfunction in SIC, and potentially offer a novel therapeutic target.

## Key facts

- **NIH application ID:** 10242849
- **Project number:** 5K08HL153784-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Brittney Williams
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $155,150
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242849

## Citation

> US National Institutes of Health, RePORTER application 10242849, Role of miRNA-TLR7 signaling in platelet activation and dysfunction in sepsis (5K08HL153784-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10242849. Licensed CC0.

---

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