# Mechanistic insights of inflammation and organ failure after trauma or critical illness

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $9,735

## Abstract

Abstract/Summary
 Aspiration of non-infectious gastro-esophageal contents and/or exposure to high concentrations of
supplemental oxygen are common events in trauma, anesthetized and/or other critically ill patients. Some of
these patients will develop a more serious and protracted pulmonary or systemic inflammatory response
leading to acute lung injury (ALI) or worse, acute respiratory distress syndrome (ARDS). Despite recent
advances in critical care medicine, overall mortality from ARDS remains unacceptably high, reflecting the lack
of specific therapies. Currently, the pathogenesis of this devastating syndrome remains incompletely
understood, particularly after the “non-infectious” or “sterile” stimuli as mentioned above. The characteristic
features of ALI/ARDS include an intense inflammatory response, severe injury to the epithelial / endothelial
barrier and alveolar edema. Recent evidence suggests that type I alveolar epithelial (ATI) cell have previously
unrecognized functions in innate immunity and are underappreciated players in lung cellcell cross-talk. Based
on our published and preliminary data, we propose that ATI cell-derived microvesicles (ATI-MVs) mediate the
intercellular communication between ATI cells and alveolar macrophages (AMs) by the shuttling of selective
miRNAs, thus broadcasting distress signals to the recipient cells and initiating the inflammatory cascades. In
our previous work, we have reported that epithelial extracellular vesicles (EVs) are inducible and detectable in
both mouse broncho-alveolar lavage fluid (BALF). After exposure to aspirated acid or hyperoxia (sterile model
of ALI), most of the induced EVs originate from living ATI epithelial cells and fall into the range of microvesicles
(MVs). We further showed that MV-shuttling miRNAs promoted classic macrophage activation and migration in
vitro and lung inflammation in vivo. Lipid raft protein caveolin-1 (cav-1) facilitates the selection of miRNA
complex in the MVs. Based on our published and the supporting data, we hypothesize that the type I alveolar
epithelial MVs mediate non-infectious stimuli-associated inflammation via promoting macrophage activation
and recruitment through MV-miRNAs. We also hypothesize that the stimuli-induced cav-1 / hnRNPA2B1
interaction and modification regulate the incorporation of selective miRNAs into MVs. We will test our
hypotheses in the following specific aims. In aim I: we will characterize the secretion of MV-miRNAs and their
target cells in the presence of non-infectious stimuli. In aim II, we will determine the mechanisms of the miRNA
selection in MVs. In aim III, we will determine the functions of MV-miRNAs after non-infectious stimuli.
 This current application is a supplemental proposal to request funds for an undergraduate student who
will be trained by us in summer and working on this project from June to August 2021.

## Key facts

- **NIH application ID:** 10393782
- **Project number:** 3R01GM127596-04S1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Yang Jin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,735
- **Award type:** 3
- **Project period:** 2018-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393782

## Citation

> US National Institutes of Health, RePORTER application 10393782, Mechanistic insights of inflammation and organ failure after trauma or critical illness (3R01GM127596-04S1). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10393782. Licensed CC0.

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