Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome.
Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome.
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腹水综合征肉鸡肺动脉的转录组分析和基因鉴定
DOI：
10.1371/journal.pone.0156045
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Yang F;Cao H;Xiao Q;Guo X;Zhuang Y;Zhang C;Wang T;Lin H;Song Y;Hu G;Liu P
肺动脉高压，也称为腹水综合征（AS），仍然是一种临床上具有挑战性的疾病，对人类和肉鸡都有很大的影响。肺动脉重构是AS发生发展的关键环节。肺动脉重构调控AS进展的确切分子机制尚不清楚。取2只AS阳性肉鸡和2只正常肉鸡的肺动脉进行RNA测序（RNA-seq）分析和病理学观察。RNA-seq分析共发现895个显著差异表达基因（DEG），其中上调基因437个，下调基因458个，显著富集到12个GO（Gene Ontology）术语和4个KEGG（京都基因和基因组百科全书）通路（Padj<0.05），这些通路调节肺动脉重构，从而导致AS的发生。这些GO术语和通路包括核糖体、Jak-STAT和NOD样受体信号通路，它们通过血管平滑肌细胞增殖、炎症和血管平滑肌细胞增殖共同调节肺动脉重构。这些通路中的一些显著DEG包括RPL 5、7、8、9、14等基因的下调; IL-6、K60、STAT 3、STAT 5 Pim 1和SOCS 3等基因的上调; IKKα、IkB、P38、5种细胞因子IL-6、IL-8、IL-1β、IL-18和MIP-1β。AS肉鸡肺动脉中CYP 1B 1、ALDH 7A 1、MYLK、CAMK 4、BMP 7和INOS等6种重要的肺动脉血管重构和结构调节因子表达上调。病理结果显示，病变组肺动脉发生重塑并变粗。我们目前的数据表明，在肉鸡AS进展的基础上，调节肺动脉重构的复杂分子回路中有一些特定的成分。我们揭示了一些有价值的候选基因和途径，参与肺动脉重塑进一步促进AS的进展。
Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS progression.