Department of Neonatology, Tianjin Central Hospital of Gynecology and Obstetrics, Nankai 3rd Road No. 156, Nankai, Tianjin, China.
Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.
Biotechnol Lett. 2020 Dec;42(12):2569-2580. doi: 10.1007/s10529-020-02986-y. Epub 2020 Aug 14.
The objective of this study was to discover unknown differentially expressed genes (DEGs) associated with bronchopulmonary dysplasia (BPD), analyze their functions and enriched signaling pathways, and identify hub genes correlating with BPD incidence and evolvement.
Of 1289 DEGs identified, 568 were downregulated and 721 were upregulated. The DEGs were mainly associated with oxidative stress, angiogenesis, extracellular matrix, inflammation, cell cycle, and protein binding. Eight DEGs were identified as hub genes, including C-X-C motif chemokine ligand 5 (Cxcl5), connective tissue growth factor (Ctgf), interleukin 6 (IL6), matrix metallopeptidase 9 (Mmp9), mitogen-activated protein kinase 14 (Mapk14), platelet and endothelial cell adhesion molecule 1 (Pecam1), TIMP metallopeptidase inhibitor 1 (Timp1), and TIMP metallopeptidase inhibitor 2 (Timp2). IL6 mRNA and protein expression levels were significantly increased in the peripheral blood of neonates with BPD.
Hence, BPD involves complex biological changes. Our findings indicate that inflammation and angiogenesis may play major roles in BPD pathogenesis and that IL6 has the potential to serve as a biomarker for early BPD diagnosis.
本研究旨在发现与支气管肺发育不良（BPD）相关的未知差异表达基因（DEG），分析其功能和富集信号通路，并鉴定与 BPD 发生率和演变相关的枢纽基因。
在鉴定的 1289 个 DEG 中，有 568 个下调，721 个上调。这些 DEG 主要与氧化应激、血管生成、细胞外基质、炎症、细胞周期和蛋白质结合有关。有 8 个 DEG 被鉴定为枢纽基因，包括 C-X-C 基序趋化因子配体 5（Cxcl5）、结缔组织生长因子（Ctgf）、白细胞介素 6（IL6）、基质金属蛋白酶 9（Mmp9）、丝裂原激活蛋白激酶 14（Mapk14）、血小板内皮细胞黏附分子 1（Pecam1）、金属蛋白酶组织抑制剂 1（Timp1）和金属蛋白酶组织抑制剂 2（Timp2）。BPD 新生儿外周血中 IL6mRNA 和蛋白表达水平显著升高。
因此，BPD 涉及复杂的生物学变化。我们的研究结果表明，炎症和血管生成可能在 BPD 发病机制中起主要作用，IL6 有可能成为早期 BPD 诊断的生物标志物。
