Pigment Epithelium–Derived Factor Mediates Impaired Lung Vascular Development in Neonatal Hyperoxia
| Autor: | Heber C. Nielsen, Daisy S. Nakamura, Ira M. Herman, Anne Chetty, Michelle Bennett, Gong-Jie Cao, S. Patricia Becerra, Sana Mujahid, Linh Dang, MaryAnn V. Volpe |
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| Rok vydání: | 2015 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Pathology Angiogenesis Clinical Biochemistry Hyperoxia Biology Cell Line Mice chemistry.chemical_compound Vasculogenesis PEDF Cell Movement Internal medicine medicine Animals Nerve Growth Factors Eye Proteins Angiostatins Lung Molecular Biology Serpins Bronchopulmonary Dysplasia Cell Proliferation Original Research Platelet Endothelial Cell Adhesion Molecule Vascular Endothelial Growth Factors Cell Biology respiratory system Mice Inbred C57BL Oxygen Platelet Endothelial Cell Adhesion Molecule-1 Endothelial stem cell Vascular endothelial growth factor Endocrinology medicine.anatomical_structure Animals Newborn chemistry Endothelium Vascular medicine.symptom |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 52:295-303 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2013-0229oc |
| Popis: | Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium–derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF−/− mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P < 0.05). In situ hybridization and immunofluorescence identified PEDF production primarily in alveolar epithelium. Hyperoxia reduced alveolarization in WT mice (P < 0.05) but not in PEDF−/− mice. WT hyperoxic mice had fewer platelet endothelial cell adhesion molecule (PECAM)-positive cells per alveolus (1.4 ± 0.4) than RA-exposed mice (4.3 ± 0.3; P < 0.05); this reduction was absent in hyperoxic PEDF−/− mice. The interactive regulation of lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors. |
| Databáze: | OpenAIRE |
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