Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients

哮喘患者支气管肺泡灌洗液外泌体中微小RNA谱的改变

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作者:Bettina Levänen, Nirav R Bhakta, Patricia Torregrosa Paredes, Rebecca Barbeau, Stefanie Hiltbrunner, Joshua L Pollack, C Magnus Sköld, Magnus Svartengren, Johan Grunewald, Susanne Gabrielsson, Anders Eklund, Britt-Marie Larsson, Prescott G Woodruff, David J Erle, Åsa M Wheelock

Background

Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge.

Conclusion

These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.

Methods

Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR.

Objective

To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure.

Results

The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q(2) = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles.

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