# Layilin as a modulator of platelet activation and thromboinflammation

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $38,703

## Abstract

Abstract
Inflammatory Bowel Disease (IBD) is characterized by inappropriate immune cell infiltration within the colon and
incidence of this disease grows annually. With currently no cure, patients can only mitigate symptoms through
surgery and immunosuppressants. An extracellular matrix component, hyaluronan (HA), is synthesized into
cable-like structures during inflammation that act as attachment sites for recruited leukocytes. Platelets bind to
these cables and degrade the HA and this capability to metabolize HA is lost during IBD. These HA fragments
have pro-inflammatory effects when released into circulation. How platelets recognize HA, however, is unknown.
Our long-term goal is to determine a potential drug target for non-invasive treatment in IBD patients by targeting
HA receptors on platelets. We have previously found that, contrary to what would be expected, the predominant
HA receptor on platelets is not CD44, but the understudied receptor, layilin. The objective of this proposal is to
utilize both human IBD patients and murine platelets to determine the role of the hyaluronan receptor, layilin, in
platelets. This receptor is downregulated in IBD patients, correlating to the well-documented platelet dysfunction
in patients. Preliminary results show that inhibiting this receptor results in loss of platelet aggregation, spreading,
and HA degradation. The central hypothesis of this proposal is that dysregulation of platelet-driven HA
metabolism enhances recruitment and activation of CD44-expressing cells, such as leukocytes, into the intestinal
microvasculature. The rationale for this project is that layilin could be a novel target for treatment of platelet
dysregulation in chronic inflammatory diseases. It may be acting as a negative regulator for platelet activation
based on our preliminary results. The central hypothesis will be tested by examining two specific aims: 1) to
determine how layilin mediates cell signaling driving platelet activation and 2) to determine the mechanism by
which layilin influences inflammation in a murine model of colitis. This approach is innovative because it targets
the understudied receptor in hyperactive platelets, a cell type not extensively investigated in disease progression
of IBD. In the final aim, we will also be utilizing platelet specific LAYN KO (PF4-Cre LAYNfl/fl) and WT mice to
produce a novel murine model for ulcerative colitis. The proposed research is significant because we anticipate
this research to develop a non-invasive treatment for thromboinflammatory diseases.

## Key facts

- **NIH application ID:** 10937996
- **Project number:** 5F31HL164091-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Rebecca Mellema
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $38,703
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937996

## Citation

> US National Institutes of Health, RePORTER application 10937996, Layilin as a modulator of platelet activation and thromboinflammation (5F31HL164091-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10937996. Licensed CC0.

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