An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans

Abstract

Severe equine asthma is an incurable obstructive respiratory condition affecting 10–15% of horses in temperate climates. Upon exposure to airborne antigens from hay feeding, affected horses show neutrophilic airway inflammation and bronchoconstriction, leading to increased respiratory effort. The resulting implications range from welfare concerns to economic impacts on equestrian sports and horse breeding. Immunological and pathophysiological characteristics of severe equine asthma show important parallels with allergic and severe neutrophilic human asthma. Our study aimed at investigating regulatory networks underlying the pathophysiology of the disease by profiling miRNA and mRNA expression in lung tissue samples from asthmatic horses compared with healthy controls. We sequenced small RNAs and mRNAs from lungs of seven asthmatic horses in exacerbation, five affected horses in remission, and eight healthy control horses. Our comprehensive differential expression analyses, combined with the miRNA–mRNA negative correlation approach, revealed a strong similarity on the transcriptomic level between severe equine asthma and severe neutrophilic asthma in humans, potentially through affecting Th17 cell differentiation. This study also showed that several dysregulated miRNAs and mRNAs are involved in airway remodeling. These results present a starting point for a better transcriptomic understanding of severe equine asthma and its similarities to asthma in humans.

In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes

“…The identification of putative gene targets of each miRNA is an important first step to start elucidating its potential functions. miRNAs usually act by either inducing degradation or repressing translation of their target mRNAs 82,83 . Even though individual miRNAs are associated with specific cell functions, it is clear that the miRNome simultaneously at any given time acts over multiple mRNAs encoding proteins with similar, opposed or intertwined roles in their respective gene networks 81 .…”

Application across species of a one health approach to liquid sample handling for respiratory based -omics analysis

“…In keeping with the One-Health-concept, the horse is widely acknowledged as an attractive model for human asthma 3 , 18 , 19 , addressing needs that cannot be addressed through small animal models: mice are widely recognised as poor models of the human immune response, particularly in relation to the lung 20 , 21 . In addition to the important similarities between horses and humans with regard to both pathophysiology and macrophage/monocyte biology, the horse also represents an ideal source of large volumes of various biological sample types 18 , 19 , 22 – 25 . For example, the volume and the associated cell retrieval rates derived from horses represent at least 2–3 orders of magnitude greater than those obtained from rodent models.…”

In Vitro CSC-derived Cardiomyocytes Exhibit the Typical microRNA-mRNA Blueprint of Endogenous Cardiomyocytes

“…Identi cation of miRNA/mRNA interactions and regulatory networks potentially modulating CSC speci cation and differentiation into cardiomyocytes The identi cation of putative gene targets of each miRNA is an important rst step to start elucidating its potential functions. miRNAs usually act by either inducing degradation or repressing translation of their target mRNAs 82,83 . Even though individual miRNAs are associated with speci c cell functions, it is clear that the miRNome simultaneously at any given time acts over multiple mRNAs encoding proteins with similar, opposed or intertwined roles in their respective gene networks 81 .…”