Alteration of Plasma Exosome Content in Acute Respiratory Distress Syndrome: a miRNA signature associated to lung fibrosing process

Abstract

Background: As diagnosis of Acute respiratory distress syndrome (ARDS) is complex, we need to develop novel molecular biomarkers for its detection. In this study, we aimed to characterize microRNA (miRNA) content of exosomes from plasma of ARDS patients and identify altered miRNAs associated to ARDS.

Methods: Exosomes were isolated from plasma of ARDS patients (n=16) and healthy donors (HD) (n=16) via standard ultracentrifugation protocol. The exosomal miRNA profiling was performed using small RNA-Sequencing technology (cohort 1: ARDS (n=7) vs HD (n=7)), and differentially expressed miRNAs were validated with quantitative RT-PCR (cohort 2: ARDS (n=9) vs HD (n=9)). Disease prediction/pathway analysis of validated miRNAs were performed using Ingenuity Pathway Analysis (IPA).

Results: Small RNA-Sequencing analysis has enabled us to identify a substantial dysregulation of plasma exosomal miRNA levels in patients with ARDS. Indeed, 9 miRNAs were differentially expressed in plasma-derived exosomes of ARDS patients compared to HD, among which 7 upregulated and 2 downregulated miRNAs. Using quantitative RT-PCR, we validated the increase of 5 plasma exosomal miRNAs (let-7b-3p, miR-233-3p, miR-24-3p, miR-23a-3p and miR-142-5p) in ARDS context. The bioinformatic analysis by IPA demonstrated that the dysregulated miRNAs are involved in the development of inflammatory disease and lung fibrosis.

Conclusion: For the first time, we identified potential biomarkers for ARDS from plasma-derived exosomes. These candidates should be investigated in large independent cohorts to confirm their biomarker status in ARDS.