Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches

Li, Yue; Lu, Xin; Dennery, Phyllis A.; Yao, Hongwei

doi:10.1016/j.redox.2021.102104

Cited by 13 publications

(3 citation statements)

References 160 publications

(207 reference statements)

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“…BPD is a chronic lung disease affecting the life and health of preterm infants [ 32 ]. Previous studies have demonstrated an association of BPD with adverse respiratory outcomes and neurodevelopmental dysfunctions in children [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrant methylation of Serpine1 mediates lung injury in neonatal mice prenatally exposed to intrauterine inflammation

et al. 2022

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Background Intrauterine inflammation (IUI) alters epigenetic modifications in offspring, leading to lung injury. However, the epigenetic mechanism underlying IUI-induced lung injury remains uncertain. In the present study, we aim to investigate the effect of IUI on lung development, and to identify the key molecule involved in this process and its epigenetic regulatory mechanism. Results Serpine1 was upregulated in the lung tissue of neonatal mice with IUI. Intranasal delivery of Serpine1 siRNA markedly reversed IUI-induced lung injury. Serpine1 overexpression substantially promoted cell senescence of both human and murine lung epithelial cells, reflected by decreased cell proliferation and increased senescence-associated β-galactosidase activity, G0/G1 cell fraction, senescence marker, and oxidative and DNA damage marker expression. IUI decreased the methylation level of the Serpine1 promoter, and methylation of the promoter led to transcriptional repression of Serpine1. Furthermore, IUI promoted the expression of Tet1 potentially through TNF-α, while Tet1 facilitated the demethylation of Serpine1 promoter. DNA pull-down and ChIP assays revealed that the Serpine1 promoter was regulated by Rela and Hdac2. DNA demethylation increased the recruitment of Rela to the Serpine1 promoter and induced the release of Hdac2. Conclusion Increased Serpine1 expression mediated by DNA demethylation causes lung injury in neonatal mice with IUI. Therefore, therapeutic interventions targeting Serpine1 may effectively prevent IUI-induced lung injury.

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Section: Discussionmentioning

confidence: 99%

Aberrant methylation of Serpine1 mediates lung injury in neonatal mice prenatally exposed to intrauterine inflammation

et al. 2022

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“…BPD is a chronic lung disease initiated by inflammation and oxidative stress during the canalicular and saccular stages of lung development, disrupting alveolar and vascular growth ( Thébaud et al, 2019 ). Mitochondrial dysfunction, impaired oxidative phosphorylation, and their downstream effects are all operative in BPD pathogenesis ( Ratner et al, 2009 ; Yue and Yao, 2016 ; Kandasamy et al, 2017 ; Shah et al, 2018 ; Xuefei et al, 2021 ; Yue et al, 2021 ). Mitochondrial density continues to increase during the postnatal period to support normal lung development and growth but mitochondrial density and function are disrupted in infants with BPD ( El-Merhie et al, 2017 ).…”

Section: Mitochondrial Dysfunction In Preterm Infants and Its Downstr...mentioning

confidence: 99%

PGC-1α activity and mitochondrial dysfunction in preterm infants

2022

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Extremely low gestational age neonates (ELGANs) are born in a relatively hyperoxic environment with weak antioxidant defenses, placing them at high risk for mitochondrial dysfunction affecting multiple organ systems including the nervous, respiratory, ocular, and gastrointestinal systems. The brain and lungs are highly affected by mitochondrial dysfunction and dysregulation in the neonate, causing white matter injury (WMI) and bronchopulmonary dysplasia (BPD), respectively. Adequate mitochondrial function is important in providing sufficient energy for organ development as it relates to alveolarization and axonal myelination and decreasing oxidative stress via reactive oxygen species (ROS) and reactive nitrogen species (RNS) detoxification. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a master regulator of mitochondrial biogenesis and function. Since mitochondrial dysfunction is at the root of WMI and BPD pathobiology, exploring therapies that can regulate PGC-1α activity may be beneficial. This review article describes several promising therapeutic agents that can mitigate mitochondrial dysfunction through direct and indirect activation and upregulation of the PGC-1α pathway. Metformin, resveratrol, omega 3 fatty acids, montelukast, L-citrulline, and adiponectin are promising candidates that require further pre-clinical and clinical studies to understand their efficacy in decreasing the burden of disease from WMI and BPD in preterm infants.

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“…The diagnosis, as per existing criteria, can only be established at the corrected age of 36 weeks, and the lack of specific treatment modalities underscores the imperative need for sensitive early biomarkers for BPD [ 3 ]. Metabolomics assays have evidenced altered glucose, lipid, and amino acid metabolism in preterm infants who develop BPD, suggesting that dysregulated glucose metabolism may serve as a predictive marker for BPD onset in preterm neonates [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Combined gestational age and serum fucose for early prediction of risk for bronchopulmonary dysplasia in premature infants

Li,

Xu,

et al. 2024

BMC Pediatr

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Objective As the predominant complication in preterm infants, Bronchopulmonary Dysplasia (BPD) necessitates accurate identification of infants at risk and expedited therapeutic interventions for an improved prognosis. This study evaluates the potential of Monosaccharide Composite (MC) enriched with environmental information from circulating glycans as a diagnostic biomarker for early-onset BPD, and, concurrently, appraises BPD risk in premature neonates. Materials and methods The study incorporated 234 neonates of ≤32 weeks gestational age. Clinical data and serum samples, collected one week post-birth, were meticulously assessed. The quantification of serum-free monosaccharides and their degraded counterparts was accomplished via High-performance Liquid Chromatography (HPLC). Logistic regression analysis facilitated the construction of models for early BPD diagnosis. The diagnostic potential of various monosaccharides for BPD was determined using Receiver Operating Characteristic (ROC) curves, integrating clinical data for enhanced diagnostic precision, and evaluated by the Area Under the Curve (AUC). Results Among the 234 neonates deemed eligible, BPD development was noted in 68 (29.06%), with 70.59% mild (48/68) and 29.41% moderate-severe (20/68) cases. Multivariate analysis delineated several significant risk factors for BPD, including gestational age, birth weight, duration of both invasive mechanical and non-invasive ventilation, Patent Ductus Arteriosus (PDA), pregnancy-induced hypertension, and concentrations of two free monosaccharides (Glc-F and Man-F) and five degraded monosaccharides (Fuc-D, GalN-D, Glc-D, and Man-D). Notably, the concentrations of Glc-D and Fuc-D in the moderate-to-severe BPD group were significantly diminished relative to the mild BPD group. A potent predictive capability for BPD development was exhibited by the conjunction of gestational age and Fuc-D, with an AUC of 0.96. Conclusion A predictive model harnessing the power of gestational age and Fuc-D demonstrates promising efficacy in foretelling BPD development with high sensitivity (95.0%) and specificity (94.81%), potentially enabling timely intervention and improved neonatal outcomes.

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Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches

Cited by 13 publications

References 160 publications

Aberrant methylation of Serpine1 mediates lung injury in neonatal mice prenatally exposed to intrauterine inflammation

Aberrant methylation of Serpine1 mediates lung injury in neonatal mice prenatally exposed to intrauterine inflammation

PGC-1α activity and mitochondrial dysfunction in preterm infants

Combined gestational age and serum fucose for early prediction of risk for bronchopulmonary dysplasia in premature infants

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