Effect of prenatal sulforaphane (SUL) on hyperoxia-induced lung injury in Nrf2+/+ and Nrf2-/- neonates
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PROVIDER: PRJNA691586 | ENA |
REPOSITORIES: ENA
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Project description:Results: Prenatal SUL altered baseline lung genes involved in organ/cell development and grow (e.g., Ibsp, Ctsk, Igfbp5) and ARE responses (e.g., Aldh3a1, Maff, Mafg) in Nrf2+/+ neonates and in cell morphogenesis and cell death and organismal injury/abnormality inhibition (e.g., Neat1, Nox4, Vegfa, Igfbp2, Trp53) in Nrf2-/- neonates. In hyperoxia-exposed lung, prenatal SULincreased organogenesis/development genes (e.g., Prss35, Cep128) and decreased inflammatory genes (H2-D1, Cd40, Lcn2, Cdh22) in Nrf2+/+ pups. In Nrf2-/- mice exposed to hyperoxia, prenatal SFN decreased hyperoxia-upregulated many immune and inflammatory response genes (e.g., Ccl9, Btla, Ncf4, Ltb, Selplg, Csf2rb) and upregulated many DNA repair/damage checkpoint genes (e.g., Uimc1, Neil3, Nbn, Smc4, Smc6). Conclusion: Overall, prenatal maternal SUL altered genes differentially in Nrf2+/+ and Nrf2-/- lungs. However, SUL-mediated transcriptome changes affected similar biological functions benificial to host defense and organ development in both strain. Compensatory differential lung transcriptome changes in Nrf2-/- neonates may resulted in the manifest protection of their severe hyperoxic lung injury.
2022-01-05 | GSE164699 | GEO
Project description:Protective roles of Nrf2, a key transcription factor for antioxidant and defense genes, have been determined in oxidative lung injury, and health benefits of Nrf2 agonists including sulforaphane have been demonstrated. The current study was designed to investigate the effect of sulforaphane on model acute lung injury and sulforaphane-mediated transcriptome changes in mouse lungs. Adult mice genetically deficient in Nrf2 (Nrf2-/-) and wild-type controls (Nrf2+/+, ICR) received oral sulforaphane (9 mmol/daily) or vehicle before (-5, -3, -1 days) hyperoxia or air exposure (3 days), and lung injury and gene expression changes were assessed. Sulforaphane significantly reduced hyperoxia-induced airway injury, inflammation, and mucus hypersecretion in Nrf2+/+ mice while relatively marginal treatment effect was found in Nrf2-/- mice. Sulforaphane significantly altered expression of lung genes associated with oxidative phosphorylation and mitochondrial dysfunction (Atp2a2, Cox7a1, Ndufa1) basally and cell function/cycle and protein metabolism (Actr1a, Wasf2, Ccne1, Gtpbp4) after hyperoxia in Nrf2+/+ mice. Nrf2-dependently modulated lung genes by sulforaphane and hyperoxia were associated with tissue development and hereditary disorders (Slc25a3, Pccb, Psmc3ip). Results demonstrate preventive roles of sulforaphane against oxidant lung injury in mice, and reveal potential downstream mechanisms. Our observations also suggest Nrf2-independent mechanisms of sulforaphane in prevention of acute lung injury.
2015-06-01 | GSE58654 | GEO
Project description:Effect of prenatal sulforaphane (SUL) on Nrf2+/+ and Nrf2-/- placenta
| PRJNA691587 | 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:Results: In Nrf2+/+ placenta, genes involved in estrogen receptor signaling and reproductive system development (e.f., Med subfamily, Igf1r, Ncor2), vasculature and embryonic development (e.g., Adamdec1, Pdgfrb, Col8a2, Sema3g, Krt5, Lce1a1), and inhibition of prenatal death and cell morbidity (e.g., Dnmt3a, Col4a2) were regulated by SFN. Multiple granzyme isozymes (Gzmd, Gzmg, Gzmf, Gzmc) and oxidoreduction genes (e.g., Gstt1, Gstt2, Prdx5, Hao3, Hsd17b10, Pecr) were suppressed in Nrf2+/+ placenta treated with SFN. SFN-altered transcriptome changes in Nrf2-/- placenta were predicted to inhibit prenatal death via regulation of genes including Igf2r, Tgfb2, Arid5b, and Il6st and to activate angiogenesis and cell growth by alteration of genes such as Timp3, Kdr, and Il6ra. Conclusion: Overall transcriptome changes indicated reduced cytotoxicity and activated feto-placenta barrier functions in both Nrf2+/+ and Nrf2-/- mice.
2022-01-05 | GSE164700 | GEO
Project description:Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to DNA-regulatory sequences near stress responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted ChIP-sequencing experiments in human BEAS-2B cell line treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates.
2018-06-19 | GSE75812 | GEO
Project description:This study aims to assess whether genes involved in central metabolism induced by Sulforaphane, SF, are mediated through the transcription factor NRF2. A time course RNA-seq experiment was performed, where RNA is extracted after 3, 9, and 24 hours SF treatment. This experiment tests the following hypotheses: 1) The transcriptional changes induced by SF at early time points will affect genes involved in the antioxidant response machinery of the cell. 2) The transcriptional changes induced by SF at 24 h will affect genes involved in central metabolism. This is a follow up from a previous study of the effect of SF on HepG2 cells under different glucose environment (see E-MTAB-12851).
2024-03-30 | E-MTAB-12858 | biostudies-arrayexpress
Project description:Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to DNA-regulatory sequences near stress responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted ChIP-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high-confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRAhas implications for response to retinoid treatments and adipogenesis. In mouse 3T3-L1 cells SFN treatment affected Rxra expression early in adipogenesis and knockdown of Nrf2 delayed Rxra expression, both leading to impaired adipogenesis. ChIP-Seq analysis of NRF2 binding sites in human lymphoblastoid cells treated with sulforaphane or vehicle
2012-06-18 | E-GEOD-37589 | biostudies-arrayexpress
Project description:We identified a SNP rs242561, located within a regulatory region of the MAPT gene (encoding microtubule-associated protein Tau). It was consistently occupied by NRF2/sMAF in multiple ChIP-seq experiments, and its strong-binding allele increased transactivation, and accorded higher mRNA levels in cell lines and human brain. To confirm the allele-specific binding, we conducted ChIP tagmentaion sequencing experiment in human lymphoblastoid cell line GM12763 which is heterozygous for rs242561. NRF2 ChIP DNA was isolated from GM12763 cells treated with Sulforaphane (SFN) in triplicates. The region containing rs242561 was amplified using primers, Fwd 5â??-AGCCTTCCCTGTCCTTGATT-3â??, Rev 5â??-GGACCGAGCTTCCAGTCTAA-3â??, and tagmentated using Tn5-based transposition for library construction. Libraries were sequenced on Illumina MiSeq. NRF2 ChIP tagmentation sequencing of a 241bp intron region in MAPT gene using GM12763 treated with sulforaphane
2016-04-14 | E-GEOD-79569 | biostudies-arrayexpress