Abstract
Eosinophil asthma is characterized by the infiltration of eosinophils to the bronchial epithelium. The toxic cationic protein released by eosinophils, mainly major basic protein (MBP), is one of the most important causative factors of epithelium damage. Poly-L-Arginine (PLA) is a kind of synthetic cationic polypeptides, which is widely used to mimic the effects of MBP on epithelial cells in vitro. However, little is known about the changes of differentially expressed genes (DEGs) and transcriptome profiles in cationic protein stimulated epithelial cells. In this study, we compared the expression of DEGs and transcriptome profiles between PLA-treated airway epithelial cells NCI-H292 and control. The results showed that there were a total of 230 DEGs, of which 86 were upregulated and 144 were downregulated. These DEGs were further analyzed using gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results showed that the upregulated DEGs were involved in cholesterol synthesis, protein binding, and composition of cellular membranes, mainly enriched in metabolic and biosynthesis pathways. While downregulated DEGs were implicated in cell adhesion, extracellular matrix (ECM) composition and cytoskeleton and were enriched in ECM pathway. In conclusion, our research provided the mechanism of the cationic polypeptides acting on the airway epithelial cells on the basis of transcriptomic profile, and this could be regarded as important indications in unveiling the pathologic role of natural cationic proteins in the damage to epithelial cells of asthmatics.
Highlights
Eosinophil cells are known to play a vital role in the pathophysiology of asthma, whose number in peripheral blood is relevant to the exacerbations of acute asthma
Considerable researches have demonstrated that Poly-L-Arginine could be regarded as a surrogate of major basic protein (MBP) to mimic the effect on airway epithelial cells
Some of differentially expressed genes (DEGs) have been reported in asthmatics before, but many novel genes and pathways which have not been linked to asthma before were displayed in our research
Summary
Eosinophil cells are known to play a vital role in the pathophysiology of asthma, whose number in peripheral blood is relevant to the exacerbations of acute asthma. Various toxic cationic proteins released by eosinophils such as major basic protein (MBP) are deemed to be essential in the etiology of asthma, especially in the pathogenesis of airway hyperresponsiveness (AHR) [2]. MBP can disrupt the epithelium in miscellaneous aspects, such as breaking the balance among ions, stimulating pulmonary edema, and directly destroying structures, as well as functions of epithelium in a charge dependent manner. Cationic protein can induce apoptosis morphology changes in a concentration dependent manner in epithelial cells [3, 4]. The destructive effects of cationic proteins on airway epithelium include the disruption of the epithelial structures, as well as their physiological functions. As the function of epithelial cells is impaired, airway smooth muscles are exposed, which result in more sensitive contractions to the agonist [6]
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