Choriodecidual Infection Downregulates Angiogenesis and Morphogenesis Pathways in Fetal Lungs from Macaca Nemestrina
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca mulatta Macaca nemestrina
PROVIDER: GSE39029 | GEO | 2013/04/23
SECONDARY ACCESSION(S): PRJNA169645
REPOSITORIES: GEO
Similar Datasets
Project description:Intrauterine exposure to amniotic fluid (AF) cytokines is thought to predispose to bronchopulmonary dysplasia (BPD). We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD. Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118-125 days gestation (term=172 days) received choriodecidual inoculation of either: 1) Group B Streptococcus (n=5) or 2) saline (n=5). Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry.
2013-04-23 | E-GEOD-39029 | biostudies-arrayexpress
Project description:Fetal lung and brain injury have been linked with intrauterine exposure to amniotic fluid (AF) cytokines, but injury to other fetal organs are not well characterized. Fetal cardiac injury was suspected based on an ultrasound study suggesting diastolic dysfunction, but not previously confirmed or characterized. In this study we explore the relationship between cytokine exposure due to exposure to group B streptococcus and cardiac gene expression.
2018-01-23 | GSE98459 | GEO
Project description:Mechanisms underlying in utero fetal lung injury remain poorly defined, and a greater understanding of pathways regulating these processes may lead to novel therapies that prevent lung injury before birth. MicroRNAs (miRNAs) are small non-coding, endogenous RNAs that regulate gene expression and have been implicated in the pathogenesis of lung disease. We sought to determine whether differentially expressed miRNAs in the fetal lung following choriodecidual infection are associated with elevation of amniotic fluid (AF) cytokine levels and acute lung injury in a nonhuman primate model. After inoculating ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118-125 days gestation (term=172 days) with either Group B Streptococcus (GBS) 1 x 106 colony forming units (n=5) or saline (n=5) in the choriodecidual space, we extracted fetal lung mRNA and miRNA and profiled changes in expression. We identified 9 differentially expressed miRNAs (p<0.05, >1.5 fold change) in the GBS-exposed fetal lungs by microarray, but of these only miR-155-5p was significantly elevated by qRT-PCR (p=0.016). The microarray log2 intensity of miR-155-5p positively correlated with fetal lung injury scores and AF IL-1? and TNF-??levels (R2=0.54, p=0.016). In situ hybridization revealed that miR-155-5p is expressed throughout the fetal lung, which led us to investigate mechanisms that regulate miR-155-5p expression. Significantly elevated miR-155-5p expression was observed when immortalized human fetal airway epithelial (FeAE) cells were exposed to IL-6 and TNF-??. Overexpression of miR-155-5p in FeAE cells increased production of IL-6, CCL5/RANTES and CXCL10/IP-10. Using a luciferase reporter assay, we validated FGF9 as an authentic target of miR-155-5p, which is essential to development of the lung mesenchyme and distal epithelial branching. Collectively, these results suggest that a choriodecidual inflammatory response leads to increased AF cytokine levels, which induce miR-155-5p expression. In turn, miR-155-5p activates and recruits leukocytes (IL-6, CCL5/RANTES) and inhibits fetal lung angiogenesis (CXCL10/IP-10), meschenchymal development and epithelial branching (targets FGF9 mRNA). A therapy to antagonize miR-155-5p may ameliorate perinatal lung injury. Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118-125 days gestation (term=172 days) received choriodecidual inoculation of either: 1) Group B Streptococcus (n=5) or 2) saline (n=5). Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry.
2015-08-05 | E-GEOD-60628 | biostudies-arrayexpress
Project description:Rationale. Lung inflammation in premature infants contributes to development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without apparent adverse effects as occur with systemic dexamethasone therapy. Objectives. To determine effects of budesonide on differential genes expression in human fetal lung
2016-06-30 | GSE83888 | GEO
Project description:Rationale. Lung inflammation in premature infants contributes to development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without apparent adverse effects as occur with systemic dexamethasone therapy. Objectives. To determine effects of budesonide on differential genes expression in human fetal lung Methods. We prepared RNA from 3 samples of human fetal lung at 23 weeks gestation before (preculture, PC) and after 4 days culture as explants with (Bud) or without (Way) budesonide (30 nM) and performed RNAseq on the 9 samples.
2016-06-30 | E-GEOD-83888 | biostudies-arrayexpress
Project description:We have discovered that GBS significantly remodels its transcriptome in response to exposure to human amniotic fluid. A large number of the affected genes are of unknown function, which means that much remains to be learned about the full influence of amniotic fluid on GBS. The majority of the observed changes in transcripts affects genes involved in basic bacterial metabolism and is connected to AF composition and nutritional requirements of the bacterium. The observation that many genes encoding adhesions are down-regulated, and genes encoding known virulence factors such as a hemolysin and a potent IL-8 proteinase are up-regulated likely have consequences for the outcome of host-pathogen interactions. Streptococcus agalactiae, serotype III strain NEM316 was grown in human amniotic fluid. Samples of bacteria were collected in mid log, late log and stationary growth phases and were used for RNA isolation for microarray analysis
2010-05-18 | E-GEOD-14456 | biostudies-arrayexpress
Project description:We have discovered that GBS significantly remodels its transcriptome in response to exposure to human amniotic fluid. A large number of the affected genes are of unknown function, which means that much remains to be learned about the full influence of amniotic fluid on GBS. The majority of the observed changes in transcripts affects genes involved in basic bacterial metabolism and is connected to AF composition and nutritional requirements of the bacterium. The observation that many genes encoding adhesions are down-regulated, and genes encoding known virulence factors such as a hemolysin and a potent IL-8 proteinase are up-regulated likely have consequences for the outcome of host-pathogen interactions.
2009-06-01 | GSE14456 | GEO
Project description:Mechanisms underlying in utero fetal lung injury remain poorly defined, and a greater understanding of pathways regulating these processes may lead to novel therapies that prevent lung injury before birth. MicroRNAs (miRNAs) are small non-coding, endogenous RNAs that regulate gene expression and have been implicated in the pathogenesis of lung disease. We sought to determine whether differentially expressed miRNAs in the fetal lung following choriodecidual infection are associated with elevation of amniotic fluid (AF) cytokine levels and acute lung injury in a nonhuman primate model. After inoculating ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118-125 days gestation (term=172 days) with either Group B Streptococcus (GBS) 1 x 106 colony forming units (n=5) or saline (n=5) in the choriodecidual space, we extracted fetal lung mRNA and miRNA and profiled changes in expression. We identified 9 differentially expressed miRNAs (p<0.05, >1.5 fold change) in the GBS-exposed fetal lungs by microarray, but of these only miR-155-5p was significantly elevated by qRT-PCR (p=0.016). The microarray log2 intensity of miR-155-5p positively correlated with fetal lung injury scores and AF IL-1? and TNF-??levels (R2=0.54, p=0.016). In situ hybridization revealed that miR-155-5p is expressed throughout the fetal lung, which led us to investigate mechanisms that regulate miR-155-5p expression. Significantly elevated miR-155-5p expression was observed when immortalized human fetal airway epithelial (FeAE) cells were exposed to IL-6 and TNF-??. Overexpression of miR-155-5p in FeAE cells increased production of IL-6, CCL5/RANTES and CXCL10/IP-10. Using a luciferase reporter assay, we validated FGF9 as an authentic target of miR-155-5p, which is essential to development of the lung mesenchyme and distal epithelial branching. Collectively, these results suggest that a choriodecidual inflammatory response leads to increased AF cytokine levels, which induce miR-155-5p expression. In turn, miR-155-5p activates and recruits leukocytes (IL-6, CCL5/RANTES) and inhibits fetal lung angiogenesis (CXCL10/IP-10), meschenchymal development and epithelial branching (targets FGF9 mRNA). A therapy to antagonize miR-155-5p may ameliorate perinatal lung injury.
2015-08-05 | GSE60628 | GEO
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:Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with high morbidity and mortality. To investigate the pathogenesis of CDH, miRNA sequencing was performed using amniotic fluid-derived extracellular vesicles (AF-EVs) and fetal lung tissue of nitrofen-induced CDH rat model.
2024-07-03 | GSE240558 | GEO