Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens.
Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens.
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肉鸡腹水综合征肺动脉重塑中 microRNA 和 mRNA 的表达失调
DOI：
10.18632/oncotarget.12888
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发表时间：
2017-01-10
期刊：
影响因子：
--
通讯作者：
Hu G
中科院分区：
文献类型：
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作者：
Liu P;Yang F;Zhuang Y;Xiao Q;Cao H;Zhang C;Wang T;Lin H;Guo X;Hu G
腹水综合征（AS），也称为肺动脉高压，仍然是一种严重影响人类和肉鸡的具有挑战性的疾病。肺动脉重构是AS发生发展的关键环节。本研究分别取AS组和对照组肉鸡肺动脉组织进行miRNA测序分析、miRNA-mRNA关联分析和病理学检查。在已知和新发现的miRNAs中共发现29个差异表达的miRNAs，其中18个上调，11个下调。通过GO（Gene Ontology）和KEGG（京都基因和基因组百科全书）分析表明，他们预测的潜在靶点涉及广泛的功能簇。miR-155、miR-23 b-3 p、miR-146 b-5 p和miR-146 b-3 p的上调与AS进展过程中肺动脉重构的发生密切相关。对miRNA-mRNAs的关联分析表明，这29个差异表达的miRNAs共调控162个差异表达的靶基因。其中，20个miRNAs与18个预测的靶基因相关，这些靶基因似乎参与了肺动脉重塑，主要涉及三个广泛的生理过程：缺氧感应反应（HIF 1a、NHE 1、STAT 5和STAT 3），内皮通透性功能障碍（CD 44、TRAF 2、CDK 2AP 1、LZTFL 1、JAZF 1、PEBP 1、LRP 1B、RPS 14和THBS 2）和炎症（MEOX 2、STAT 5、STAT 3、IRF 8、MAP 3 K8、IL-1 β和TNFRSF 1B）。在本研究中，一致观察到AS肉鸡的病理性肺动脉重构。总之，目前的分析进一步阐明了AS进展的肺动脉重构的分子机制。
Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs. Their predicted potential targets were involved in a wide range of functional clusters as indicated via GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. The upregulation of miR-155, miR-23b-3p, miR-146b-5p and miR-146b-3p were found closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. The association analysis for the miRNAs-mRNAs showed that these 29 significantly differentially expressed miRNAs regulate 162 differentially expressed target genes. Among them, 20 miRNAs correlated with 18 predicted target genes that appear to be involved in pulmonary artery remodeling, mainly in three broad physiological processes: the hypoxia sensing response (HIF1a, NHE1, STAT5 and STAT3), endothelial permeability dysfunction (CD44, TRAF2, CDK2AP1, LZTFL1, JAZF1, PEBP1, LRP1B, RPS14 and THBS2) and inflammation (MEOX2, STAT5, STAT3, IRF8, MAP3K8, IL-1BETA and TNFRSF1B). Pathological pulmonary artery remodeling in the AS broilers was consistently observed in the present study. Taken together, the current analysis further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression.