Dysregulation of pulmonary elastin synthesis and assembly in preterm lambs with chronic lung disease
| Autor: | Liwen Xu, Daniel D. Swartz, Marlene Rabinovitch, Robert Ertsey, Katalin Csiszar, Keith S. K. Fong, Richard D. Bland, Karen A. Wynn, Vasantha H.S. Kumar, Rita M. Ryan, Kurt H. Albertine |
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| Rok vydání: | 2007 |
| Předmět: |
Pulmonary and Respiratory Medicine
Vascular Endothelial Growth Factor A Pathology medicine.medical_specialty Platelet-derived growth factor Receptor Platelet-Derived Growth Factor alpha Physiology medicine.medical_treatment Gestational Age chemistry.chemical_compound Pregnancy Tropoelastin Physiology (medical) medicine Serine Animals Humans Respiratory system Lung Bronchopulmonary Dysplasia Peroxidase Mechanical ventilation Platelet-Derived Growth Factor Sheep biology Pancreatic Elastase business.industry Respiratory disease Infant Newborn Gene Expression Regulation Developmental Cell Biology respiratory system medicine.disease Respiration Artificial Vascular Endothelial Growth Factor Receptor-2 respiratory tract diseases Oxygen medicine.anatomical_structure Bronchopulmonary dysplasia chemistry Animals Newborn Lung disease Immunology biology.protein Female business Elastin Elastic fiber |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 292(6) |
| ISSN: | 1040-0605 |
| Popis: | Failed alveolar formation and excess, disordered elastin are key features of neonatal chronic lung disease (CLD). We previously found fewer alveoli and more elastin in lungs of preterm compared with term lambs that had mechanical ventilation (MV) with O2-rich gas for 3 wk (MV-3 wk). We hypothesized that, in preterm more than in term lambs, MV-3 wk would reduce lung expression of growth factors that regulate alveolarization (VEGF, PDGF-A) and increase lung expression of growth factors [transforming growth factor (TGF)-α, TGF-β1] and matrix molecules (tropoelastin, fibrillin-1, fibulin-5, lysyl oxidases) that regulate elastin synthesis and assembly. We measured lung expression of these genes in preterm and term lambs after MV for 1 day, 3 days, or 3 wk, and in fetal controls. Lung mRNA for VEGF, PDGF-A, and their receptors (VEGF-R2, PDGF-Rα) decreased in preterm and term lambs after MV-3 wk, with reduced lung content of the relevant proteins in preterm lambs with CLD. TGF-α and TGF-β1expression increased only in lungs of preterm lambs. Tropoelastin mRNA increased more with MV of preterm than term lambs, and expression levels remained high in lambs with CLD. In contrast, fibrillin-1 and lysyl oxidase-like-1 mRNA increased transiently, and lung abundance of other elastin-assembly genes/proteins was unchanged (fibulin-5) or reduced (lysyl oxidase) in preterm lambs with CLD. Thus MV-3 wk reduces lung expression of growth factors that regulate alveolarization and differentially alters expression of growth factors and matrix proteins that regulate elastin assembly. These changes, coupled with increased lung elastase activity measured in preterm lambs after MV for 1–3 days, likely contribute to CLD. |
| Databáze: | OpenAIRE |
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