Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain
Summary: Acute hypoxia (HX) causes extensive cellular damage in the developing human cerebral cortex. We found increased expression of activated-EGFR in affected cortical areas of neonates with HX and investigated its functional role in the piglet, which displays a highly evolved, gyrencephalic brai...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-12-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220309639 |
| _version_ | 1818439550022713344 |
|---|---|
| author | Panagiotis Kratimenos Evan Z. Goldstein Ioannis Koutroulis Susan Knoblach Beata Jablonska Payal Banerjee Shadi N. Malaeb Surajit Bhattacharya M. Isabel Almira-Suarez Vittorio Gallo Maria Delivoria-Papadopoulos |
| author_facet | Panagiotis Kratimenos Evan Z. Goldstein Ioannis Koutroulis Susan Knoblach Beata Jablonska Payal Banerjee Shadi N. Malaeb Surajit Bhattacharya M. Isabel Almira-Suarez Vittorio Gallo Maria Delivoria-Papadopoulos |
| author_sort | Panagiotis Kratimenos |
| collection | DOAJ |
| description | Summary: Acute hypoxia (HX) causes extensive cellular damage in the developing human cerebral cortex. We found increased expression of activated-EGFR in affected cortical areas of neonates with HX and investigated its functional role in the piglet, which displays a highly evolved, gyrencephalic brain, with a human-like maturation pattern. In the piglet, HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation, and reversed HX-induced astrogliosis. We performed for the first time high-throughput transcriptomic analysis of the piglet cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in piglet and human brain injury. Our results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain. |
| first_indexed | 2024-12-14T17:58:14Z |
| format | Article |
| id | doaj.art-47be4abbcf6445059095a33d92ed3cc3 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T17:58:14Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-47be4abbcf6445059095a33d92ed3cc32022-12-21T22:52:30ZengElsevieriScience2589-00422020-12-012312101766Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet BrainPanagiotis Kratimenos0Evan Z. Goldstein1Ioannis Koutroulis2Susan Knoblach3Beata Jablonska4Payal Banerjee5Shadi N. Malaeb6Surajit Bhattacharya7M. Isabel Almira-Suarez8Vittorio Gallo9Maria Delivoria-Papadopoulos10Center for Neuroscience Research, Children's National Research Institute, Children's National Hospital, George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue, NW, Washington, DC 20010 P 202-476-5922, USA; Department of Pediatrics, Division of Neonatology, Children's National Hospital and George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue, NW, Washington, DC 20010 P 202-602-4889, USA; Corresponding authorCenter for Neuroscience Research, Children's National Research Institute, Children's National Hospital, George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue, NW, Washington, DC 20010 P 202-476-5922, USADepartment of Pediatrics, Division of Emergency Medicine, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Research Center for Genetic Medicine, Children's National Research Institute, Washington, DC, USA; Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USAResearch Center for Genetic Medicine, Children's National Research Institute, Washington, DC, USA; Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USACenter for Neuroscience Research, Children's National Research Institute, Children's National Hospital, George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue, NW, Washington, DC 20010 P 202-476-5922, USAResearch Center for Genetic Medicine, Children's National Research Institute, Washington, DC, USADepartment of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USAResearch Center for Genetic Medicine, Children's National Research Institute, Washington, DC, USADepartment of Pathology, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC, USACenter for Neuroscience Research, Children's National Research Institute, Children's National Hospital, George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue, NW, Washington, DC 20010 P 202-476-5922, USA; Corresponding authorDepartment of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USASummary: Acute hypoxia (HX) causes extensive cellular damage in the developing human cerebral cortex. We found increased expression of activated-EGFR in affected cortical areas of neonates with HX and investigated its functional role in the piglet, which displays a highly evolved, gyrencephalic brain, with a human-like maturation pattern. In the piglet, HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation, and reversed HX-induced astrogliosis. We performed for the first time high-throughput transcriptomic analysis of the piglet cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in piglet and human brain injury. Our results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain.http://www.sciencedirect.com/science/article/pii/S2589004220309639Porcine Molecular BiologyDevelopmental NeuroscienceTranscriptomics |
| spellingShingle | Panagiotis Kratimenos Evan Z. Goldstein Ioannis Koutroulis Susan Knoblach Beata Jablonska Payal Banerjee Shadi N. Malaeb Surajit Bhattacharya M. Isabel Almira-Suarez Vittorio Gallo Maria Delivoria-Papadopoulos Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain iScience Porcine Molecular Biology Developmental Neuroscience Transcriptomics |
| title | Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain |
| title_full | Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain |
| title_fullStr | Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain |
| title_full_unstemmed | Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain |
| title_short | Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain |
| title_sort | epidermal growth factor receptor inhibition reverses cellular and transcriptomic alterations induced by hypoxia in the neonatal piglet brain |
| topic | Porcine Molecular Biology Developmental Neuroscience Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220309639 |
| work_keys_str_mv | AT panagiotiskratimenos epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT evanzgoldstein epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT ioanniskoutroulis epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT susanknoblach epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT beatajablonska epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT payalbanerjee epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT shadinmalaeb epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT surajitbhattacharya epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT misabelalmirasuarez epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT vittoriogallo epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain AT mariadelivoriapapadopoulos epidermalgrowthfactorreceptorinhibitionreversescellularandtranscriptomicalterationsinducedbyhypoxiaintheneonatalpigletbrain |