Introduction and objectives Idiopathic Pulmonary Fibrosis (IPF) has limited therapeutic options and predicting the natural history in individual cases is difficult. Exosomes are extracellular microvesicles that are involved in cell-cell signalling. MicroRNA isolated from exosomes has been implicated in several fibrotic models.1 At present the role of miRNAs in development of lung fibrosis is unclear. We aim to characterise miRNAs isolated from IPF patients and relate these to measures of disease severity.
Methods We assessed exosomes isolated from the serum of IPF patients (n = 8) and aged matched healthy controls (n = 6). Exosomes were characterised by western blot and Nanosight technology. MiRNA was isolated from these exosomes and profiled using a miRNA PCR assay. Demographic and clinical data was extracted from clinical records. IPF patients were stratified by radiological severity, GAP scoring and rate of progression.
Results Exosomes isolated from IPF patients demonstrated decreased fold regulation in antifibrotic miRNA such as miR-141 and miR-29 in addition to increases in fibrogenic miRNA such as miR-7 when compared to healthy controls. The degree of up regulation in miR-7 correlates significantly with stratified burden of disease. Interestingly down regulation of miR-155 was also found which has been previously associated with up regulation in mice fibrosis models. Patients had a median follow up of 31 months (IQR 17–43). There was a significant correlation with regards to up regulation of miR-125b with milder disease defined by the GAP score and preservation of FVC.
Conclusion This data identifies novel biomarkers that may provide insights into the natural history and pathogenesis of the disease. Furthermore miR-7 and miR-29 have been implicated in extracellular matrix remodelling with target genes including ECM proteins such as collagens, fibrillins and elastin. Inhibiting up regulated miRNA or supplementing down regulated miRNA may be potential therapeutic targets.
Reference 1 Jiang X, Tsitsiou E, Herrick SE, et al. MicroRNAs and the regulation of fibrosis. FEBS J. 2010;277:2015–2021
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