Regenerative Signatures in Bronchioalveolar Lavage of Acute Respiratory Distress Syndrome

This study aimed to identify potential regenerative niches by characterizing the differentially expressed proteins in the exosomes of bronchoalveolar lavage (BAL) in ARDS patients. <bold>Methods</bold> Exosomes were purified from BAL samples obtained from ARDS patients participating in the NIH-supported trials. The quantification of exosomal proteins/peptides was performed using liquid chromatography-mass spectrometry (LC-MS). Exosomal proteins that are differentially expressed between healthy controls and patients were analyzed to determine their functional annotations, cell origins, signaling pathways, networks, and clinical correlations. The findings indicate a higher number of exosomal proteins were detected in the lungs of patients with late-stage ARDS patients. Immune cells and lung epithelial stem cells were significant contributors to the composition of BAL exosomes originating from other organs. A diverse array of functions, stem cell signals, growth factors, and immune niches were augmented in both mild and severe patients. The proteins that exhibited differential expression were found to be linked with important clinical variables. Significant variations in protein-protein interaction, RNA crosstalk, and epigenetic network were noted between the mild and severe groups. Furthermore, alveolar type 2 epithelial cells have the potential to function as both exosome donors and recipients through autocrine and paracrine mechanisms. This study has identified new exosomal proteins linked to various functions, signaling pathways, and cell origins in ARDS lavage samples.