Serum exosomes from IPF patients display a fibrotic miRNA profile and induce collagen production in vitro.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease, characterised by excessive extracellular matrix deposition and compromised gas exchange. This results in the loss of lung function. Exosomes are extracellular microvesicles that are involved in cell-cell signalling due to their ability to transport proteins and RNA molecule between cells; thereby allowing cells to exert biological functions at distant sites. They have been shown to exacerbate disease in cancer, infection, and recently, fibrotic disease. Therefore, the focus of this study was to examine isolated exosomes from the serum of IPF patients. This would allow us to elucidate the contents of these vesicles, and to possibly identify a novel biomarker for IPF. Exosomes were isolated from the serum of IPF patients (n=10) and age matched healthy controls (n=6), characterised by western blot and Nanosight technology. MicroRNA was isolated from these exosomes and was profiled using a miRNA PCR array. Exosomes isolated from IPF patients showed a decrease in antifibrotic miRNAs such as miR‑141, 200b and 19b and an increase in fibrosis progressing miRNAs such as miR-125b when compared to healthy controls. These exosomes were then used to treat lung epithelial cells and fibroblasts to assess their effects on fibrotic markers such as collagen production. IPF exosomes increased collagen production as compared to exosomes from healthy controls. We also found that CD63 the exosomal marker was differentially glycosylated in IPF exosomes as compared to healthy control exosomes. This may play a role in exosome function in IPF. This data illustrates the role of exosomes in the exacerbation of fibrotic lung disease and identifies new potential biomarkers and targets for intervention.