Pulmonary vascular disease is evident in gene regulation of experimental bronchopulmonary dysplasia

被引:4
作者
Revhaug, Cecilie [1 ,2 ]
Zasada, Magdalena [3 ]
Rognlien, Anne Gro W. [1 ,2 ]
Gunther, Clara-Cecilie [4 ]
Grabowska, Agnieszka [5 ]
Ksiazek, Teofila [5 ]
Madetko-Talowska, Anna [5 ]
Szewczyk, Katarzyna [5 ]
Bik-Multanowski, Mirolaw [5 ]
Kwinta, Przemko [3 ]
Pietrzyk, Jacek J. [3 ,5 ]
Baumbusch, Lars O. [2 ]
Saugstad, Ola D. [1 ,2 ]
机构
[1] Univ Oslo, Dept Pediat Res, Oslo, Norway
[2] Natl Hosp Norway, Oslo Univ Hosp, Dept Pediat Res, Oslo, Oslo, Norway
[3] Jagiellonian Univ, Inst Pediat, Fac Med, Dept Pediat,Med Coll, Krakow, Poland
[4] Norwegian Comp Ctr, Oslo, Norway
[5] Jagiellonian Univ, Inst Pediat, Fac Med, Dept Med Genet,Med Coll, Krakow, Poland
关键词
Bronchopulmonary dysplasia; gene regulation; pulmonary hypertension; pulmonary vascular disease; vascular tone; PRETERM INFANTS; PREMATURE-INFANTS; ADULT SURVIVORS; HYPERTENSION; RECEPTOR; INHIBITION; EXPRESSION; MUSCLE; MOUSE;
D O I
10.1080/14767058.2018.1541081
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To examine the gene expression regarding pulmonary vascular disease in experimental bronchopulmonary dysplasia in young mice. Premature delivery puts babies at risk of severe complications. Bronchopulmonary dysplasia (BPD) is a common complication of premature birth leading to lifelong affection of pulmonary function. BPD is recognized as a disease of arrested alveolar development. The disease process is not fully described and no complete cure or prevention is known. The focus of interest in the search for treatment and prevention of BPD has traditionally been at airspace level; however, the pulmonary vasculature is increasingly acknowledged in the pathology of BPD. The aim of the investigation was to study the gene expression in lungs with BPD with regards to pulmonary vascular disease (PVD). Methods: We employed a murine model of hyperoxia-induced BPD and gene expression microarray technique to determine the mRNA expression in lung tissue from young mice. We combined gene expression pathway analysis and analyzed the biological function of multiple single gene transcripts from lung homogenate to study the PVD relevant gene expression. Results: There were n = 117 significantly differentially regulated genes related to PVD through down-regulation of contractile elements, up- and down-regulation of factors involved in vascular tone and tissue-specific genes. Several genes also allowed for pinpointing gene expression differences to the pulmonary vasculature. The gene Nppa coding for a natriuretic peptide, a potent vasodilator, was significantly down-regulated and there was a significant up-regulation of Pde1a (phosphodiesterase 1A), Ptger3 (prostaglandin e receptor 3), and Ptgs1 (prostaglandin-endoperoxide synthase one). Conclusion: The pulmonary vasculature is affected by the arrest of secondary alveolarization as seen by differentially regulated genes involved in vascular tone and pulmonary vasculature suggesting BPD is not purely an airspace disease. Clues to prevention and treatment may lie in the pulmonary vascular system.
引用
收藏
页码:2122 / 2130
页数:9
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