Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia
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PROVIDER: PRJNA679602 | ENA |
REPOSITORIES: ENA
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Project description:Preterm infants with bronchopulmonary dysplasia (BPD) have lifelong increased risk of respiratory morbidities associated with environmental pathogen exposure and underlying mechanisms are poorly understood. The resident immune cells of the lung play vital roles in host defense. However, the effect of perinatal events associated with BPD on pulmonary-specific immune cells is not well understood. We used a double-hit model of BPD induced by prenatal chorioamnionitis followed by postnatal hyperoxia, and performed global transcriptome analysis of all resident pulmonary immune cells. This is the first comprehensive report delineating transcriptomic changes in resident immune cells of the lung in a translationally relevant double-hit model of BPD.
2021-01-19 | GSE161836 | GEO
Project description:Sequential exposure to histological chorioamnionitis and postnatal hyperoxia induces alterations in gene expression and molecular pathways in neonatal cord blood monocytes, affecting immune regulation, which could potentially contribute to the pathogenesis of short- and long-term diseases in neonates. We have used microarray to find the global gene expression in neonatal cord blood monocytes exposed to either histological chorioamnionitis (HCA) or hyperoxia or both compared to control samples (no-HCA)
2026-09-03 | GSE346094 | GEO
Project description:Bronchopulmonary dysplasia (BPD) arises from a combination of prenatal and postnatal environmental factors, but the impact of prenatal inflammation on subsequent postnatal lung injury remains unclear. We aimed to investigate how prenatal lipopolysaccharide (LPS)-induced chorioamnionitis alters the composition of resident pulmonary immune cells and modifies the response to hyperoxia-induced lung injury in neonatal rats. Pregnant Sprague-Dawley rats received intra-amniotic injections of LPS or normal saline (NS) at embryonic day 20. Pups were euthanized on postnatal day 1 (P1) or exposed to 85% oxygen (O₂) or room air (RA) for 14 days and euthanized on postnatal day 14 (P14) for analysis. Resident pulmonary immune cells were quantified by flow cytometry. Mann–Whitney and ANOVA tests were used for group comparisons (p<0.05). mRNA from pulmonary immune cells collected on P1 was subjected to RNA sequencing and differential gene expression analysis. On P1, prenatal LPS exposure did not change the overall percentage of CD45⁺ pulmonary immune cells but decreased the percentages of CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, and CD45R⁺ B cells compared with the NS+RA group. In contrast, CD161⁺ NK cells and CD43⁺ monocytes were significantly increased. Upregulated genes were enriched in inflammatory biological processes. By P14, cell composition in the LPS+RA group normalized. However, a second insult with postnatal hyperoxia resulted in an increased proportion of CD161⁺ NK cells in the LPS+O₂ group only and an increased proportion of CD43⁺ monocytes in the NS+O₂ group only, with a relative reduction in monocytes in the LPS+O₂ group at P14. In this rat model of BPD, LPS-mediated in-utero inflammation primes neonatal lung immune cells for a dysregulated response to postnatal hyperoxia. Dual prenatal and postnatal injuries result in persistent elevation of NK cells and reduction of monocytes, while other immune subsets respond differentially, suggesting that prenatal events condition the neonatal lung immune system in ways that may influence BPD pathogenesis.
2026-07-21 | GSE338797 | GEO
Project description: Not available
| S-EPMC7808307 | biostudies-literature
Project description:Sequential Exposure to Histological Chorioamnionitis and Postnatal Hyperoxia Alters Gene Expression in Cord Blood Monocytes
| PRJNA1522932 | ENA
Project description:Background: Nrf2 is an essential cytoprotective transcription factor. However, association of Nrf2 in organ development and neonatal disease is rarely examined. Hyperoxia exposure to newborn rodents generates pulmonary phenotypes which resemble bronchopulmonary dysplasia (BPD) of prematurity. Methods: To investigate the role of Nrf2 in lung maturation and BPD pathogenesis, Nrf2-deficient (Nrf2-/-) and wild-type (Nrf2+/+) neonates were exposed to air or hyperoxia (O2). Transcriptome analysis determined Nrf2-directed mechanisms in premature lung. Lung injury was assessed by bronchoalveolar lavage analysis and histopathology. Results: In Nrf2-/- neonates, basal expression of cell cycle machinery, redox balance, and lipid/carbohydrate metabolism genes were suppressed while immunity genes were overexpressed compared to Nrf2+/+ pups. O2-induced mortality and pulmonary inflammation/injury were significantly higher in Nrf2-/- than in Nrf2+/+. Lung DNA lesion and oxidation were greater in Nrf2-/- than in Nrf2+/+, constitutively and after O2. Nrf2-dependent genes modulated cellular growth/proliferation, defense, immunity, and lipid metabolism against hyperoxia. Bioinformatic elucidation of Nrf2 binding motifs and augmented O2-induced inflammation in genetically deficient neonates validated Gpx2 and Marco as Nrf2 effectors. Conclusion: Overall, Nrf2 in underdeveloped lungs orchestrated cell cycle, morphogenesis, and immunity as well as cellular defense constitutively and under oxidant stress. Results provide putative molecular mechanisms of Nrf2-directed lung alveolarization and BPD of prematurity. PARALLEL study design with 42 samples comparing 14 groups of age (P1 to P4 corresponding to day 0 to day 3 animals), gene, and exposure: (4 groups Nrf+/+ wild type P1-P4 air exposure) (4 groups Nrf -/- knockout P1-P4 air exposure), (3 groups Nrf+/+ wild type P2-P4 with 100 percent O2 (hyperoxia exposure) and 3 groupsNrf -/- knockout P2-P4 with 100 percent O2 (hyperoxia exposure)) Biological replicates: 3 per group
2012-05-24 | E-GEOD-29632 | biostudies-arrayexpress
Project description:Background: Nrf2 is an essential cytoprotective transcription factor. However, association of Nrf2 in organ development and neonatal disease is rarely examined. Hyperoxia exposure to newborn rodents generates pulmonary phenotypes which resemble bronchopulmonary dysplasia (BPD) of prematurity. Methods: To investigate the role of Nrf2 in lung maturation and BPD pathogenesis, Nrf2-deficient (Nrf2-/-) and wild-type (Nrf2+/+) neonates were exposed to air or hyperoxia (O2). Transcriptome analysis determined Nrf2-directed mechanisms in premature lung. Lung injury was assessed by bronchoalveolar lavage analysis and histopathology. Results: In Nrf2-/- neonates, basal expression of cell cycle machinery, redox balance, and lipid/carbohydrate metabolism genes were suppressed while immunity genes were overexpressed compared to Nrf2+/+ pups. O2-induced mortality and pulmonary inflammation/injury were significantly higher in Nrf2-/- than in Nrf2+/+. Lung DNA lesion and oxidation were greater in Nrf2-/- than in Nrf2+/+, constitutively and after O2. Nrf2-dependent genes modulated cellular growth/proliferation, defense, immunity, and lipid metabolism against hyperoxia. Bioinformatic elucidation of Nrf2 binding motifs and augmented O2-induced inflammation in genetically deficient neonates validated Gpx2 and Marco as Nrf2 effectors. Conclusion: Overall, Nrf2 in underdeveloped lungs orchestrated cell cycle, morphogenesis, and immunity as well as cellular defense constitutively and under oxidant stress. Results provide putative molecular mechanisms of Nrf2-directed lung alveolarization and BPD of prematurity.
2012-05-25 | GSE29632 | GEO
Project description:Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm infants born at less than 28 weeks gestation. Most existing clinical prediction models for BPD show limited accuracy in predicting BPD development when validated using external data, stressing the need for novel biomarkers to identify at-risk infants for early and effective interventions. We leveraged existing frozen umbilical cord blood samples from the Northwestern University Cord Blood Biobank (NUCord) to perform parallel transcriptional and DNA methylation profiling. Chorioamnionitis-associated differentially expressed genes (DEGs) in our cohort included markers previously established in clinical and animal BPD studies, such as genes related to NF-κB signaling and immune responses. Importantly, these genes were highly associated with chorioamnionitis infection status specifically in preterm infants. We also identified that BPD development is associated with disrupted methylation signatures in microRNA genes and genes associated with glucose metabolism. Our results suggest that BPD development and chorioamnionitis are associated with distinct transcriptomic and epigenetic signatures when compared with healthy term and preterm infants. These signatures may represent biomarkers measurable at birth that predict BPD development during a time window when preventative or therapeutic interventions could be applied.
2026-05-18 | GSE302178 | GEO
Project description:Background: Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, with dysmorphic microvascular development being a key factor in the pathogenesis of BPD. WNT5A plays a role in angiogenesis and vascular development and is closely associated with lung disease. However, the role and mechanism of WNT5A in hyperoxia-induced pulmonary microvascular impairment remain unclear. Methods: A hyperoxia exposure mouse model (85% oxygen for 14 days) simulating preterm BPD was used, and was sampled on postnatal day (P) 3, 7, and 14. Western blot (WB) was used to detect the expression of endothelial cell markers von Willebrand factor (vWF) and WNT5A. Mouse pulmonary microvascular endothelial cells (PMVECs) and human umbilical vein endothelial cells (HUVECs) were cultured in 85% oxygen for 48 hours. WNT5A expression and secretion were measured through WB and ELISA. WNT5A inhibitors or recombinant WNT5A (rWNT5A) were co-cultured with cells, and the cell function was assessed. Total RNA was extracted from PMVECs, followed by RNA sequencing. Results: WNT5A expression was decreased in the lungs of hyperoxia-exposed mice at P7. Consistently, in vitro hyperoxia exposure reduced WNT5A expression and its downstream effector CaMKIIγ in endothelial cells compared with normoxia-exposed controls. Both WNT5A inhibition and rWNT5A changed the migration and tube formation functions of HUVECs in normoxic and hyperoxic conditions. RNA sequencing revealed differentially expressed genes (DEGs), and suggested enrichment in the ErbB, MAPK, and Hippo pathways in the hyperoxia group. Conclusions: Hyperoxia decreased the WNT5A expression and impaired endothelial cell function potentially through WNT5A-CaMKIIγ.
2026-05-27 | GSE320519 | GEO
Project description:Background: Bronchopulmonary dysplasia (BPD), the most common complication of extreme preterm birth, can be caused by oxygen-related lung injury and is characterized by impaired alveolar and vascular development. Mesenchymal stromal cells (MSCs) have lung protective effects. Conversely, BPD is associated with increased MSCs in tracheal aspirates. Objective: To determine whether endogenous lung (L-)MSCs are perturbed in a well-established oxygen-induced rat model mimicking BPD features. Methods: Rat pups were exposed to room air or 95% oxygen from birth to postnatal day 10. On day 12, CD146+ L-MSCs were isolated and characterized according to the International Society for Cellular Therapy criteria. Epithelial and vascular repair potential were tested by scratch assay and endothelial network formation respectively, immune function by mixed lymphocyte reaction assay. Microarray analysis was performed using the Affymetrix GeneChip and gene set enrichment analysis (GSEA) software. Results: CD146+ L-MSCs isolated from rat pups exposed to hyperoxia had decreased CD73 expression and inhibited lung endothelial network formation. CD146+ L-MSCs indiscriminately promoted epithelial wound healing and limited T-cell proliferation. Expression of potent anti-angiogenic genes of the axonal guidance cue and CDC42 pathways was increased after in vivo hyperoxia, whereas genes of the anti-inflammatory JAK/STAT and lung/vascular growth promoting Fibroblast Growth Factor (FGF) pathways were decreased. Conclusions: In vivo hyperoxia exposure alters the pro-angiogenic effects and FGF expression of L-MSCs. Additionally, decreased CD73 and JAK/STAT expression suggest decreased immune function. L-MSC function may be perturbed and contribute to BPD pathogenesis. These findings may lead to improvements in manufacturing exogenous MSCs with superior repair capabilities.
2017-06-03 | GSE99633 | GEO