Oncotarget

Research Papers: Pathology:

Angiogenesis-related genes may be a more important factor than matrix metalloproteinases in bronchopulmonary dysplasia development

Min Yang, Bo-Lin Chen, Jian-Bao Huang, Yan-Ni Meng, Xiao-Jun Duan, Lu Chen, Lin-Rui Li and Yan-Ping Chen _

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Oncotarget. 2017; 8:18670-18679. https://doi.org/10.18632/oncotarget.14722

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Abstract

Min Yang1, Bo-Lin Chen2, Jian-Bao Huang1, Yan-Ni Meng1, Xiao-Jun Duan1, Lu Chen1, Lin-Rui Li1 and Yan-Ping Chen1

1 Respiratory Department 2, Hunan Children’s Hospital, Changsha, Hunan, China

2 Thoracic Medicine Department 2, Hunan Cancer Hospital, Changsha, Hunan, China

Correspondence to:

Yan-Ping Chen, email:

Keywords: bronchopulmonary dysplasia, chronic lung disease, premature infant, THBS1, MMPs, Pathology Section

Received: June 27, 2016 Accepted: January 03, 2017 Published: January 18, 2017

Abstract

We characterized the expression profile of angiogenesis-related genes (ARG) and matrix metalloproteinase (MMP) genes in preterm infants, with and without bronchopulmonary dysplasia (BPD). We reanalyzed a gene expression dataset for preterm infants from the Gene Expression Omnibus database using the Gene-Cloud of Biotechnology Information platform. A total of 1,652 genes were differentially (1.2-fold change) expressed: 811 were highly expressed in infants with BPD, and 841 were highly expressed in those without BPD. Twenty-eight and 11 ARGs were upregulated in infants with and without BPD, respectively. Among 27 detected MMPs and TIMPs, MMP8, MMP9, MMP25, TIMP2 and TIMP3 were differently expressed. Levels of THBS1, MMP8, MMP9, MMP25, TIMP2 and TIMP3 increased as severity of BPD and retinopathy of prematurity (ROP) increased, whereas ETS1, LEF1 and SPOCK2 exhibited the opposite trend. Expression of ETS1 and LEF1 had a fitting rate of R2 = 0.849 and P < 0.001. ELISAs showed a positive correlation between THBS1 and CD36 (receptor of THBS1) levels in serum samples from preterm infants. Our study indicates that the upregulation of THBS1 and downregulation of ETS1, LEF1 promotes BPD in preterm infants by disrupting blood vessel formation rather than by dysregulation of MMPs and TIMPs.


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