Home
|
Inbox
|
Search
|
View Abstract
Gender Specific Response of the Neonatal Lung to Postnatal Injury
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A6972 - Gender Specific Response of the Neonatal Lung to Postnatal Injury
Author Block: P. S. Oak1, M. Koschlig1, T. Pritzke1, K. Foerster2, P. Ahnert3, A. Windhorst4, T. Reicherzer2, H. Ehrhardt5, A. Hilgendorff6; 1Comprehensive Pneumology Center, Helmholtz Zentrum, Munich, Germany, 2Dr. von Hauner Children`s Hospital, Perinatal Center Grosshadern, Ludwig-Maximilians-University, Munich, Germany, 3Institute for Medical Informatics, Statistics, and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany, 4Institute for Medical Informatics, Justus-Liebig-University, Giessen, Germany, 5Department of General Pediatrics and Neonatology, Justus-Liebig-University and Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany, 6Comprehensive Pneumology Center, Helmholtz Zentrum Muenchen, Munich, Germany.
Rationale: Underlined by alveolar and vascular growth arrest neonatal chronic lung
disease (nCLD) is a condition arising in preterm infants subjected to prolonged
mechanical ventilation (MV) and hyperoxia (O2). Owing to the differences in
hormonal levels, a gender specific male-dominated response is known for acute
postnatal respiratory distress as well as later, nCLD. Our study targets molecular
differences in male as well as female mice and preterm infants subjected to MV-O2
that leads to functional consequences implicating on alveolar septation and lung
matrix composition.
Methods and Results: In a preclinical model of newborn mouse ventilation (5-7 day
old C57Bl/6 and PDGF-Rα+/- mice), we confirmed the critical role of PDGF-Rα
expression and signaling for disease development induced by MV and O2
(FiO2=0.4). Associated with reduced VEGF expression and increased endothelial
cell apoptosis, we showed that the TGF-β dependent downregulation of PDGF-Rα
signaling was significantly enhanced in male mice. In line with this, reduction of
myofibroblast migration in response to TGF-β is greater in male newborn mice,
supported by gender-specific effects observed in SNP and protein analysis in
preterm infants diagnosed with nCLD.
Conclusion: In a unique pre-clinical mouse model confirmed by studies in nCLD
patients, we provide data forming the molecular basis of the gender specific effects
in nCLD development indicating a critical role of PDGF-dependent myofibroblast
function.
Author Block: P. S. Oak1, M. Koschlig1, T. Pritzke1, K. Foerster2, P. Ahnert3, A. Windhorst4, T. Reicherzer2, H. Ehrhardt5, A. Hilgendorff6; 1Comprehensive Pneumology Center, Helmholtz Zentrum, Munich, Germany, 2Dr. von Hauner Children`s Hospital, Perinatal Center Grosshadern, Ludwig-Maximilians-University, Munich, Germany, 3Institute for Medical Informatics, Statistics, and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany, 4Institute for Medical Informatics, Justus-Liebig-University, Giessen, Germany, 5Department of General Pediatrics and Neonatology, Justus-Liebig-University and Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany, 6Comprehensive Pneumology Center, Helmholtz Zentrum Muenchen, Munich, Germany.
Rationale: Underlined by alveolar and vascular growth arrest neonatal chronic lung
disease (nCLD) is a condition arising in preterm infants subjected to prolonged
mechanical ventilation (MV) and hyperoxia (O2). Owing to the differences in
hormonal levels, a gender specific male-dominated response is known for acute
postnatal respiratory distress as well as later, nCLD. Our study targets molecular
differences in male as well as female mice and preterm infants subjected to MV-O2
that leads to functional consequences implicating on alveolar septation and lung
matrix composition.
Methods and Results: In a preclinical model of newborn mouse ventilation (5-7 day
old C57Bl/6 and PDGF-Rα+/- mice), we confirmed the critical role of PDGF-Rα
expression and signaling for disease development induced by MV and O2
(FiO2=0.4). Associated with reduced VEGF expression and increased endothelial
cell apoptosis, we showed that the TGF-β dependent downregulation of PDGF-Rα
signaling was significantly enhanced in male mice. In line with this, reduction of
myofibroblast migration in response to TGF-β is greater in male newborn mice,
supported by gender-specific effects observed in SNP and protein analysis in
preterm infants diagnosed with nCLD.
Conclusion: In a unique pre-clinical mouse model confirmed by studies in nCLD
patients, we provide data forming the molecular basis of the gender specific effects
in nCLD development indicating a critical role of PDGF-dependent myofibroblast
function.
|
Home
|
Inbox
|
Search
|