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整合 miRNA-mRNA 表达分析揭示了严重马哮喘和人类特定哮喘表型之间引人注目的转录组相似性。

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

机构信息

Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.

Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.

出版信息

Genes (Basel). 2020 Sep 28;11(10):1143. doi: 10.3390/genes11101143.

DOI:10.3390/genes11101143
PMID:32998415
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7600650/
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.

摘要

严重马气喘是一种无法治愈的阻塞性呼吸道疾病,影响 10-15%的温带气候下的马匹。在接触到干草喂养产生的空气传播抗原后,受影响的马匹表现出中性粒细胞性气道炎症和支气管收缩,导致呼吸努力增加。由此产生的影响范围从福利问题到对马术运动和赛马繁殖的经济影响。严重马气喘的免疫学和病理生理学特征与人类过敏和严重中性粒细胞性气喘表现出重要的相似性。我们的研究旨在通过比较哮喘马和健康对照马的肺组织样本中 miRNA 和 mRNA 的表达,来研究疾病病理生理学的调控网络。我们对 7 例哮喘发作期马、5 例缓解期马和 8 例健康对照马的肺组织中的小 RNA 和 mRNAs 进行了测序。我们的综合差异表达分析,结合 miRNA-mRNA 负相关方法,揭示了严重马气喘和人类严重中性粒细胞性气喘在转录组水平上的高度相似性,这可能是通过影响 Th17 细胞分化实现的。本研究还表明,几个失调的 miRNA 和 mRNAs 参与了气道重塑。这些结果为更好地理解严重马气喘及其与人类气喘的相似性提供了一个起点。

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