Airway Epithelial Derived Exosomes on Protecting and Remodeling of the Lung

Exosomes have recently gained interest due to their emerging role in inter-cellular communication, immune modulation, and as potential biomarkers. We hypothesize that exosomes derived from human tracheo-bronchial airway cells are diverse, carry distinct proteins and miRNA that provide intercellular signaling between different types of airway epithelial cells and therefore, remodel the biological functions of the airways. Two airway epithelial cells, HBE and Calu3 were used. Exosomes were isolated from the apical secretions and characterized by light scattering, EM, proteomic and Nanoparticle Tracking Analysis. RNA was extracted and deep sequencing and bioinformatic analyzed the expression profiles. The exosome derived from HBE and Calu3, had typical cup shaped morphology and measured 162 and 109 nm in radius, respectively. Mass spectrometry showed that HBE and Calu3 exosomes carry distinct proteins, like MUC4 in HBE and MUC13 in Calu3. Switching exosomes between HBE and Calu3 altered the protein expression and miRNA profile and quantity of the recipient cells. Further miRNA analysis indicated significantly altered expression of certain miRs such as miR-21 increased in Calu3, miR-10a-5p decreased in HBE. We previously showed that exosomes in the airway can play a role in the innate defense. Here we show that exosomes released from HTBE and Calu3 can transmit the information between different types of airway cells and provides inter-cellular communication via their small non-coding RNA and protein content and may play an important role in airway biology and epithelial remodeling.