ROLE OF ENDOPLASMIC RETICULUM STRESS IN IMPAIRED NEONATAL LUNG GROWTH AND BRONCHOPULMONARY DYSPLASIA
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ABSTRACT:
PROVIDER: PRJNA810082 | ENA |
REPOSITORIES: ENA
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Project description:Myeloperoxidase (MPO), oxidative stress (OS), and endoplasmic reticulum (ER) stress are all increased in the lungs of neonatal rat pups raised in hyperoxia (HOX, >90% O2), an established model of bronchopulmonary dysplasia (BPD). However, the relationship between OS, MPO, and ER stress has not been examined in HOX rat pups. To determine the relationship between OS, MPO, and ER stress in BPD we treated Sprague-Dawley neonatal rat pups with Tunicamycin (Tun) or with HOX. Tun directly induces ER stress and simplifies neonatal lung alveolarization. Previously, we showed that HOX induces a cycle of destruction that we hypothesize through increased OS, MPO, and ER stress to induce BPD. To inhibit ER stress specifically, we used tauroursodeoxycholic acid (TUDCA), a molecular chaperone. To break the cycle of destruction and reduce OS and MPO we used N-acetyl-lysyltyrosylcysteine-amide (KYC), a systems pharmacology agent. Lung structure was studied morphometrically. ER stress was detected using immunofluorescence (IF), transcriptomic, proteomic, and electron microscopic analyses. Increased ER stress was observed in the lungs of HOX rat pups and also in human BPD lungs by IF. Morphometric and proteomic studies of rat lungs showed that Tun treatment decreased lung complexity and increased ER stress and BPD severity. The fact that TUDCA improved lung complexity in Tun-treated neonatal rat pups, and decreased BPD induced by HOX provides strong support for the idea that ER stress plays a causal role in BPD. Additional support comes from data showing TUDCA decreased lung myeloid cells and MPO levels in the lungs of both Tun- and HOX-treated neonatal rat pups. These data link OS and MPO to ER stress in the mechanisms mediating BPD. KYC's effective inhibition of ER stress in the lungs of Tun-treated rat pups provides additional support for the idea that MPO-induced ER stress plays a direct causal role in BPD. Thus, ER stress appears to expand our proposed cycle of destruction. Our results suggest ER stress evolves from OS and MPO to increase neonatal lung injury and impaired neonatal lung growth and development. The encouraging effect of TUDCA indicates chemical chaperone has the potential in treating BPD. Using multiomic data to investigate the role of endoplasmic reticulum stress in the development of BPD in rat model.
2022-08-11 | GSE197403 | GEO
Project description:Background: Metabolic dysregulation has been implicated in bronchopulmonary dysplasia development. Taurine is an essential amino acid for neonates and is critically involved in glucose and fatty acid metabolism. Neonatal tissue obtains taurine mainly through the taurine transporter. The biological role of taurine in neonatal lung development has never been explored. As glucose metabolism mechanistically modulates angiogenesis and angiogenesis is the central player for neonatal lung development, we hypothesize that taurine depletion contributes to bronchopulmonary dysplasia development. Results: Although most genes and proteins for oxidative phosphorylation were enriched in hyperoxia pup lungs, the complex-1 activity decreased. The decrease in taurine-dependent complex-1 core subunits, ND5 and ND6, in hyperoxia lungs reasonably explained the discrepancy. Metabolomics analysis demonstrated decreased lung taurine with increased blood taurine of hyperoxia pups, compatible with the decreased taurine transporter expression. Decreased glycosylation and increased degradation explained the decreased taurine transporter expression. The results of the complementary study using tunicamycin and tauroursodeoxycholic acid studies supported that endoplasmic reticulum stress contributes to decreased taurine transporter expression in hyperoxia lungs. The effect of taurine treatment on reducing endoplasmic reticulum stress, increasing ND5 and ND6 expression, angiogenesis, and, most importantly, the alveolar formation is beneficial to hyperoxia rat pups. Conclusion: Hyperoxia exposure causes endoplasmic reticulum stress, increases taurine transporter degradation, and leads to taurine depletion in the neonatal lungs with subsequent metabolic dysregulation, resulting in poor alveolar formation of the neonatal lungs. We provide evidence of the never-being-reported protective role of taurine in neonatal lung development. The fact that taurine attenuates the severity of bronchopulmonary dysplasia by reducing hyperoxia-induced endoplasmic reticulum stress and mitochondrial dysfunction indicates its therapeutic potential for treating bronchopulmonary dysplasia.
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Project description:Microbiome features of bronchopulmonary dysplasia
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Project description:We performed miRNA and mRNA profiling at postnatal day 14 and day 29 to compare hyperoxia-induced bronchopulmonary dysplasia and wild type. We built potential miRNA-mRNA interaction networks specific to brochopulmonary dysplasia. Replicated time course of mouse lung development at 2 time points (P14, P29). Three replicates per time point for bronchopulmonary dysplasia induced by hyperoxia mouse lung, and two replicates per time point for wild type mouse lung. This dataset represents the mRNA expression profiling component of the study.
2012-04-30 | E-GEOD-25286 | biostudies-arrayexpress
Project description:We performed miRNA and mRNA profiling at postnatal day 14 and day 29 to compare hyperoxia-induced bronchopulmonary dysplasia and wild type. We built potential miRNA-mRNA interaction networks specific to brochopulmonary dysplasia. Replicated time course of mouse lung development at 2 time points (P14, P29). Three replicates per time point for bronchopulmonary dysplasia induced by hyperoxia mouse lung, and two replicates per time point for wild type mouse lung. This dataset represents the miRNA profiling component of the study.
2012-05-01 | E-GEOD-25290 | biostudies-arrayexpress
Project description:In order to study the gene expression changes in neonatal bronchopulmonary dysplasia (BPD) induced by hyperoxia, we used a rat model to detect the gene expression changes in the control group (A) and hyperoxia group (O) after birth.
2022-08-29 | GSE212098 | GEO
Project description:We performed miRNA and mRNA profiling at postnatal day 14 and day 29 to compare hyperoxia-induced bronchopulmonary dysplasia and wild type. We built potential miRNA-mRNA interaction networks specific to brochopulmonary dysplasia.
2012-05-01 | GSE25290 | GEO
Project description:We performed miRNA and mRNA profiling at postnatal day 14 and day 29 to compare hyperoxia-induced bronchopulmonary dysplasia and wild type. We built potential miRNA-mRNA interaction networks specific to brochopulmonary dysplasia.
2012-05-01 | GSE25286 | GEO
Project description:The juxtaposition of Taurine in Bronchopulmonary Dysplasia
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Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore differentially expressed genes associated with BPD. Cord blood mRNA from preterm neonates that went on to develop BPD (n = 6) or not (nonBPD, n = 17) was applied to Illumina HumanHT-12 arrays, we identify differentially expressed genes associated with BPD.
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