Identification of key pathways and differentially expressed genes in bronchopulmonary dysplasia using bioinformatics ana

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ORIGINAL RESEARCH PAPER

Identification of key pathways and differentially expressed genes in bronchopulmonary dysplasia using bioinformatics analysis Weiheng Yan . Miaomiao Jiang . Jun Zheng

Received: 4 May 2020 / Accepted: 8 August 2020 Ó Springer Nature B.V. 2020

Abstract Objectives 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. Results 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

Weiheng Yan and Miaomiao Jiang contributed equally to the work. W. Yan  M. Jiang  J. Zheng (&) Department of Neonatology, Tianjin Central Hospital of Gynecology and Obstetrics, Nankai 3rd Road No. 156, Nankai, Tianjin, China e-mail: [email protected] W. Yan  M. Jiang  J. Zheng Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China

metallopeptidase inhibitor 2 (Timp2). IL6 mRNA and protein expression levels were significantly increased in the peripheral blood of neonates with BPD. Conclusions 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. Keywords Bioinformatics analysis  Bronchopulmonary dysplasia  IL6  Neonatal  Transcriptome

Introduction Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that frequently occurs in premature infants, especially in very premature or very-lowbirth-weight infants (VLBWIs) (Pasha et al. 2018). BPD was first described by Northway et al. in 1967 (Northway et al. 1967). With advances in perinatal medicine, the rate of successful treatment of BPD in premature infants has increased. Nevertheless, premature infants have extremely immature organ development, and respiratory insufficiency remains the main factor that contributes to perinatal morbidity and mortality (Jung et al. 2017). Since most VLBWIs are born during the saccular stage of lung development,

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which is critical for lung development, BPD can cause abnormal lung development and affect lifelong lung function (Principi et al. 2018). In addition, BPD can cause damage to nervous system and other systemic organs (Abman et al. 2017). However, the underlying pathogenesis of BPD is no