# The Role of Pericytes in the Vascular Dysfunction of Sepsis

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $103,300

## Abstract

PROJECT SUMMARY/ABSTRACT
 Septic shock with multiple organ failure is the leading cause of death in non-coronary intensive care units
and remains a major health problem in the US. Endothelial cell (EC) dysfunction, manifested by increases in
vascular permeability, is an important hallmark of septic shock and plays a critical role in the pathogenesis of
multi-organ failure. Pericytes maintain endothelial barrier function and represent a potential therapeutic target in
sepsis. However, the processes that govern pericyte viability and their role in barrier function in sepsis have not
yet been fully elucidated. Pericytes are specialized cells embedded in the capillary basement membrane that
wrap around endothelial cells of the microcirculation throughout the body and are thought to be important
regulators of microcirculatory homeostasis. However, the role of pericytes in the endothelial dysfunction of sepsis
is largely unknown. Our data demonstrated that pericytes are depleted in the mouse lung and kidney
microvasculature during cecal ligation and puncture (CLP)-induced sepsis and pericyte depletion results in
vascular leakage. The transcription factor friend leukemia virus integration 1 (Fli-1), is critical to pericyte
dysfunction and viability in sepsis by mediating pericyte programmed cell death through pyroptosis. MiR-145
inhibits Fli-1 expression and is abundantly expressed in pericytes; however, during sepsis, miR-145 expression
decreases with a concomitant increase in Fli-1 expression. This suggests that miR-145 may play an important
role in pericyte viability and, therefore, be an important regulator of vascular permeability. A clearer
understanding of how the miR-145/Fli-1 axis regulates pericyte viability in sepsis in a critical gap in knowledge
that may lead to novel therapeutic approaches for sepsis. Furthermore, understanding the mechanisms by which
pericytes support the vascular barrier integrity in sepsis may also have therapeutic implications. One potential
mechanism whereby pericytes communicate with endothelial cells is through paracrine signaling via exosomes.
Intriguingly, we have demonstrated that pericyte-derived exosomes but not fibroblast-derived exosomes improve
survival in mice subjected to CLP-induced sepsis and that pericyte exosomes contain abundant miR-145. The
long-term goal of our research is to identify novel treatment strategies to maintain endothelial barrier function in
sepsis. The overall objective for this proposal is to identify the determinants of pericyte viability in sepsis and the
mechanisms by which pericytes maintain endothelial barrier function. We hypothesize that pericyte viability
regulated by the miR-145/Fli-1 axis is a critical determinant of sepsis outcomes through pericyte-
mediated stabilization of endothelial permeability. Three specific aims address this hypothesis: Aim 1:
Determine the mechanisms by which the miR-145/Fli-1 axis regulates pericyte function and viability in sepsis.
Aim 2: Define ...

## Key facts

- **NIH application ID:** 10225689
- **Project number:** 3R01GM130653-03S1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Hongkuan Fan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $103,300
- **Award type:** 3
- **Project period:** 2018-09-21 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225689

## Citation

> US National Institutes of Health, RePORTER application 10225689, The Role of Pericytes in the Vascular Dysfunction of Sepsis (3R01GM130653-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225689. Licensed CC0.

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