A Blood Exosomal miRNA Signature in Acute Respiratory Distress Syndrome

Gilles Parzibut; Monique Henket; Catherine Moermans; Ingrid Struman; Edouard Louis; Michel Malaise; Renaud Louis; Benoît Misset; Makon-Sébastien Njock; Julien Guiot

doi:10.3389/fmolb.2021.640042

A Blood Exosomal miRNA Signature in Acute Respiratory Distress Syndrome

Front Mol Biosci. 2021 Jul 15:8:640042. doi: 10.3389/fmolb.2021.640042. eCollection 2021.

Authors

Gilles Parzibut¹, Monique Henket², Catherine Moermans², Ingrid Struman³, Edouard Louis^{4

5}, Michel Malaise^{5

6}, Renaud Louis^{2

5}, Benoît Misset¹, Makon-Sébastien Njock^{2

4

5

6}, Julien Guiot^{1

2

5}

Affiliations

¹ Department of Intensive Care, University Hospital of Liège, Liège, Belgium.
² Laboratory of Pneumology, GIGA Research Center, University of Liège, University Hospital of Liège, Liège, Belgium.
³ Laboratory of Molecular Angiogenesis, GIGA Research Center, University of Liège, Liège, Belgium.
⁴ Laboratory of Gastroenterology, GIGA Research Center, University of Liège, University Hospital of Liège, Liège, Belgium.
⁵ Fibropole Research Group, University Hospital of Liège, Liège, Belgium.
⁶ Laboratory of Rheumatology, GIGA Research Center, University of Liège, University Hospital of Liège, Liège, Belgium.

Abstract

Acute respiratory distress syndrome (ARDS) is a diffuse, acute, inflammatory lung disease characterized by a severe respiratory failure. Recognizing and promptly treating ARDS is critical to combat the high mortality associated with the disease. Despite a significant progress in the treatment of ARDS, our ability to identify early patients and predict outcomes remains limited. The development of novel biomarkers is crucial. In this study, we profiled microRNA (miRNA) expression of plasma-derived exosomes in ARDS disease by small RNA sequencing. Sequencing of 8 ARDS patients and 10 healthy subjects (HSs) allowed to identify 12 differentially expressed exosomal miRNAs (adjusted p < 0.05). Pathway analysis of their predicted targets revealed enrichment in several biological processes in agreement with ARDS pathophysiology, such as inflammation, immune cell activation, and fibrosis. By quantitative RT-PCR, we validated the alteration of nine exosomal miRNAs in an independent cohort of 15 ARDS patients and 20 HSs, among which seven present high capability in discriminating ARDS patients from HSs (area under the curve > 0.8) (miR-130a-3p, miR-221-3p, miR-24-3p, miR-98-3p, Let-7d-3p, miR-1273a, and miR-193a-5p). These findings highlight exosomal miRNA dysregulation in the plasma of ARDS patients which provide promising diagnostic biomarkers and open new perspectives for the development of therapeutics.

Keywords: acute lung injury; acute respiratory distress syndrome; diagnostic biomarkers; exosomes; fibrosis; inflammation; microRNAs.