Gene Expression Profiling in Preterm Infants: New Aspects of Bronchopulmonary Dysplasia Development

Pietrzyk, Jacek J; Kwinta, Przemko; Wollen, Embjørg J.; Bik-Multanowski, Mirosław; Madetko‐Talowska, Anna; Günther, Clara‐Cecilie; Jagła, Mateusz; Tomasik, Tomasz; Saugstad, Ola Didrik

doi:10.1371/journal.pone.0078585

Cited by 59 publications

(62 citation statements)

References 45 publications

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“…6, we minimized subject-and age-related variations in expression measurement and modeled global gene-specific developmental expression patterns via probe-wise nonparametric regression (Text E1) (18). The normalized datasets represent individual smoothened trajectories for every gene modeled at 35 distinct postconception ages (54-127 dpc) spanned by 139 samples of S1 (19,666 unique genes), and 23 distinct ages (53 to 130 dpc) spanned by 28 samples of GSE14334 (20,361 unique genes). We limited both datasets to 17,929 common genes.…”

Section: Clinical Relevancementioning

confidence: 99%

“…Next, we investigated the relationships between G1-G3 and sex-DEG with genes related to BPD, asthma, fetal lung development (positive control), and postexercise neutrophils (negative control) from other published studies (Text E1 differentially expressed in peripheral blood leukocytes from 68 patients with BPD relative to 43 control patients at Days 5, 14, or 28 after birth from GSE32472 (19). GSE32472 and dataset S2 used the same microarray platform, cf (Table E5).…”

Section: Sex Differences In the Developing Human Fetal Lung And Theirmentioning

confidence: 99%

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Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Kho

Chhabra

Sharma

et al. 2016

Am J Respir Cell Mol Biol

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The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases. We analyzed whole-lung transcriptome profiles of 61 females and 78 males at 54-127 days postconception (dpc) from nonsmoking mothers using unsupervised principal component analysis and supervised linear regression models. We identified dominant transcriptomic correlates for postconception age and sex with corresponding gene sets that were enriched for developing lung structural and functional ontologies. We observed that the transcriptomic sex difference was not a uniform global time shift/lag, rather, lungs of males appear to be more mature than those of females before 96 dpc, and females appear to be more mature than males after 96 dpc. The age correlate gene set was consistently enriched for asthma and bronchopulmonary dysplasia genes, but the sex correlate gene sets were not. Despite sex differences in the developing fetal lung transcriptome, postconception age appears to be more dominant than sex in the effect of early fetal lung developments on disease risk during this early pseudoglandular phase of development.

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Section: Clinical Relevancementioning

confidence: 99%

Section: Sex Differences In the Developing Human Fetal Lung And Theirmentioning

confidence: 99%

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Kho

Chhabra

Sharma

et al. 2016

Am J Respir Cell Mol Biol

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“…This study identified both general mast cell (tryptase) and mucosal-type mast cell specific (CPA3) markers increased in BPD tissue. Pietrzyk et al 96 carried out genome wide transcriptional profiling of RNA extracted from peripheral blood mononuclear cells of BPD subjects and non-BPD controls followed by pathway enrichment analysis. They found that the expression of nearly 10% of the genome was altered in BPD infants, mostly in the cell cycle pathway and T cell signaling pathway.…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers, Early Diagnosis, and Clinical Predictors of Bronchopulmonary Dysplasia

Lal

Ambalavanan

2015

Clinics in Perinatology

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Bronchopulmonary Dysplasia (BPD) continues to be an important source of morbidity and mortality in premature neonates. The phenotype of BPD is extremely variable, and diagnosis is a clinical operational definition. A number of clinical and laboratory biomarkers have been proposed for the early identification of infants at higher risk of this disease, to characterize disease activity and severity and for determination of prognosis. Clinical prediction models for BPD have been developed using birth weight, gestational age, indicators of respiratory illness severity, and other clinical variables. Other biomarkers of BPD include those based on imaging of the lungs, lung function measures, and measurements of various analytes in different body fluids (blood, tracheal aspirates, exhaled breath condensates, urine, etc). Novel systems biology ‘omic’ based approaches including but not limited to genomics, proteomics, metabolomics and microbiomics are required for evaluating the multiple interacting cellular and molecular networks that control lung development and injury in BPD. Here we present a critical evaluation of the biomarker approaches studied in the diagnosis of BPD and highlight the future avenues for research in this field.

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“…BPD is a complex disease influenced by interactions between genetic factors, fetal environment and postnatal risk-factors that contribute to lung injury (2,20). While pulmonary oxidative stress is implicated in neonatal lung injury the relationships between anti-oxidant stress response sequence variants and BPD remain understudied (3,4).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants

et al. 2014

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Background Lung injury resulting from oxidative stress contributes to bronchopulmonary dysplasia (BPD) pathogenesis. Nuclear factor erythroid-2 related factor-2 (NFE2L2) regulates cytoprotective responses to oxidative stress by inducing enzymes containing anti-oxidant response elements (ARE). We hypothesized that ARE genetic variants will modulate susceptibility or severity of BPD in very low birth weight (VLBW) infants. Methods Blood samples obtained from VLBW infants were used for genotyping variants in the SOD2, NFE2L2, GCLC, GSTP1, HMOX1 and NQO1 genes. SNPs were genotyped utilizing TaqMan probes (Applied Biosystems (ABI), Grand Island, NY), and data was analyzed using the ABI HT7900. Genetic dominance and recessive models were tested to determine associations between SNPs and BPD. Results In our cohort (n=659), 284 infants had BPD; 135 of whom developed severe BPD. Presence of the hypomorphic NQO1 SNP (rs1800566) in a homozygous state was associated with increased BPD while presence of the NFE2L2 SNP (rs6721961) was associated with decreased severe BPD in the entire cohort and in Caucasian infants. In regression models that adjusted for epidemiological confounders, the NQO1 and the NFE2L2 SNPs were associated with BPD and severe BPD, respectively. Conclusions Genetic variants in NFE2L2-ARE axis may contribute to the variance in liability to BPD observed in preterm infants. These results require confirmation in independent cohorts.

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Gene Expression Profiling in Preterm Infants: New Aspects of Bronchopulmonary Dysplasia Development

Cited by 59 publications

References 45 publications

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Biomarkers, Early Diagnosis, and Clinical Predictors of Bronchopulmonary Dysplasia

Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants

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