Increased Apoptosis and Expression of p21 and p53 in Premature Infant Baboon Model of Bronchopulmonary Dysplasia

Das, Kumuda C.; Ravi, Dashnamoorthy; Holland, William

doi:10.1089/152308604771978417

Cited by 37 publications

(38 citation statements)

References 36 publications

(52 reference statements)

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“…Pathway analysis of genes in the G2 and BPD overlap showed that the most enriched pathways included the p53 signaling pathway and the complement and coagulation cascades. Previous studies have demonstrated a role for p53 in the development of BPD (30). Among the genes identified in this analysis GTSE1, THBS1, and SERPINE1 act downstream from p53.…”

Section: Discussionmentioning

confidence: 68%

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: Discussionmentioning

confidence: 68%

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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“…One common histologic feature is the accumulation of apoptotic neutrophils, epithelial, or parenchymal cells in the inflamed tissues (11,12). This observation is unexpected as apoptotic cells are removed rapidly in healthy adults.…”

mentioning

confidence: 99%

Clearance of Apoptotic Neutrophils Is Diminished in Cord Blood Monocytes and Does Not Lead to Reduced IL-8 Production

et al. 2009

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Phagocytosis of apoptotic cells, e.g., neutrophils, by monocytes is essential for resolution of inflammation. Delayed removal leads to secondary necrosis, perpetuating inflammation, and tissue destruction. Common histologic features in neonatal chronic inflammatory disorders are an accumulation of apoptotic cells in inflamed tissues. We hypothesized that apoptotic cell removal by monocytes is compromised in newborns. PKH-26 labeled autologous or allogeneic apoptotic neutrophils were fed to monocytes of adult donors (PBMO) and cord blood (CBMO), and phagocytic activity was analyzed by flow cytometry and confocal microscopy. Relative mRNA-expression levels of 21 surface receptors and bridging molecules relevant for apoptotic cell removal were measured, as was postphagocytic IL-8 production upon LPS-stimulation. Compared with PBMO, CBMO exhibited a significantly diminished phagocytotic competence for autologous and allogeneic apoptotic neutrophils. mRNA-expression levels of milk fat globule-EGF factor 8 and T cell immunoglobulin-and mucin-domain-containing molecule, two crucial members of the phagocytic synapse of apoptotic cell removal, were reduced in CBMO. In PBMO, interaction with autologous apoptotic neutrophils reduced LPS-induced IL-8 production whereas it was enhanced in CBMO. Our data suggest a specific defect in CBMO during clearance of apoptotic neutrophils resulting in impaired anti-inflammatory capacity. (Pediatr Res 66: 507-512, 2009) P hagocytosis of apoptotic cells by monocytes is a crucial step for normal tissue homeostasis by removing invaded immune cells, e.g., neutrophils, from inflamed tissue (1,2). Delayed removal may lead to secondary necrosis of the apoptotic cell, thus perpetuating inflammation and consecutive tissue destruction. Apart from a safe disposal of apoptotic debris, monocytes secrete anti-inflammatory signals, whereas inflammatory reactions are suppressed, hence enforcing the resolution of inflammation (1). Engulfment is mediated through receptors on the phagocyte, which can either bind structures on the apoptotic cell directly or by the help of bridging molecules, such as mucin-domain-containing molecule E8 (MFG-E8), which form a "phagocytic synapse" (reviewed in Ref. 1).During the neonatal period, tissue damage often results in chronic inflammatory responses such as bronchopulmonary dysplasia (BPD), periventricular leucomalacia (PVL), or necrotising enterocolitis (NEC) (3-10). One common histologic feature is the accumulation of apoptotic neutrophils, epithelial, or parenchymal cells in the inflamed tissues (11,12). This observation is unexpected as apoptotic cells are removed rapidly in healthy adults. One reason could be that neonatal monocytes do not engulf apoptotic cells as efficiently as their adult counterparts. Although neonatal monocytes show functional differences compared with those from adults (13), they are not impaired in their phagocytic competence for Grampositive (14) or Gram-negative bacteria in vitro (15,16).Therefore, we investigated whether neonat...

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“…(Adapted from Schafer FQ et al, 2001) The link between redox potential and BPD can be explained by an exacerbated apoptosis rate caused by an abnormally elevated redox potential (Luyet et al, 2000). Lung samples from premature baboons with BPD (Das et al, 2004) showed a large number of apoptotic events. In newborn guinea pigs given parenteral nutrition for 4 days, the alveolar count was 20% lower when the nutritive solution was infused without light protection, peroxide concentration being higher in light-exposed solutions (Section 5.2 below) (Lavoie et al, , 2005(Lavoie et al, , 2008.…”

Section: Redox Potential Of Glutathionementioning

confidence: 97%

Bronchopulmonary Dysplasia: The Role of Oxidative Stress

Lavoie¹,

Mohamed²

2012

Lung Diseases - Selected State of the Art Reviews

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Increased Apoptosis and Expression of p21 and p53 in Premature Infant Baboon Model of Bronchopulmonary Dysplasia

Cited by 37 publications

References 36 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

Clearance of Apoptotic Neutrophils Is Diminished in Cord Blood Monocytes and Does Not Lead to Reduced IL-8 Production

Bronchopulmonary Dysplasia: The Role of Oxidative Stress

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