epidermal-growth-factor and Bronchopulmonary-Dysplasia

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Disease Models, Animal; Epidermal Growth Factor; Fibroblast Growth Factors; Growth Substances; Humans; Infant, Newborn; Lung; Platelet-Derived Growth Factor; Respiratory Distress Syndrome, Newborn; Somatomedins; Transforming Growth Factor alpha; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

BackgroundDeficiency of vascular endothelial growth factor (VEGF) is associated with hypoplastic lung diseases, such as congenital diaphragmatic hernia. Provision of VEGF has been demonstrated to be beneficial in hyperoxia-induced bronchopulmonary dysplasia, and hence could induce lung growth and improve the outcome in hypoplastic lung diseases. We aimed to determine the effects of exogenous VEGF in a rodent model of compensatory lung growth after left pneumonectomy.MethodsEight-to-ten-week-old C57Bl6 male mice underwent left pneumonectomy, followed by daily intra-peritoneal injections of saline or VEGF (0.5 mg/kg). Lung volume measurement, pulmonary function tests, and morphometric analyses were performed on post-operative day (POD) 4 and 10. The pulmonary expression of angiogenic factors was analyzed by quantitative polymerase chain reaction and western blot.ResultsLung volume on POD 4 was higher in the VEGF-treated mice (P=0.03). On morphometric analyses, VEGF increased the parenchymal volume (P=0.001), alveolar volume (P=0.0003), and alveolar number (P<0.0001) on POD 4. The VEGF group displayed higher levels of phosphorylated-VEGFR2/VEGFR2 (P=0.03) and epidermal growth factor (EGF) messenger RNA (P=0.01).ConclusionVEGF accelerated the compensatory lung growth in mice, by increasing the alveolar units. These changes may be mediated by VEGFR2 and EGF-dependent mechanisms.

Topics: Animals; Bronchopulmonary Dysplasia; Epidermal Growth Factor; Hyperoxia; Lung; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Organ Size; Organogenesis; Pneumonectomy; Pulmonary Alveoli; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Cells staining for immunoreactive human epidermal growth factor were sought in the lungs and tracheas of human fetuses from 8 to 24 weeks of gestation. Lungs of liveborn infants from 25 to 40 weeks of gestation (stillborn to 7 months postnatal life), both with and without lung pathology, were also studied. In the early fetal trachea (12 to 15 weeks), many nonciliated cells immunostained for immunoreactive human epidermal growth factor in the lining epithelium. By 16 weeks of gestation this widespread staining was replaced by stained nonciliated single cells or small clusters of cells which were identifiable until 24 weeks. In the few tracheas which were available from liveborn infants who died without evidence of lung disease, stained cells were seldom identified in the lining epithelium after 24 weeks of gestation. In contrast, from 18 weeks until term, tracheal submucosal glands contained scattered cells which immunostained for immunoreactive human epidermal growth factor but which did not appear to be classical mucous cells. Beginning at 20 weeks of gestation, positively staining cells were found occasionally in bronchial lining epithelium, but more often in bronchial submucosal glands. Immunostained cells were never identified in bronchiolar epithelium in normal fetal or newborn lungs. In liveborn infants from 24 weeks onward who developed lung disease, many tracheas were severely damaged. In the presence of extensive denudation of the mucosa or the development of squamous metaplasia, immunostained cells were rarely seen in the lining epithelium. However, even under these conditions stained glandular cells could usually be identified. Stained cells were also present in the necks of those tracheal glands from which new epithelial lining cells appeared to be migrating onto denuded surfaces. Immunostained cells in the bronchial lining epithelium of infants with chronic lung disease were infrequent, just as they were in the fetus, but bronchial submucosal glands contained positively stained cells similar to those in tracheal glands. The appearance and distribution of immunostained cells were similar in the tracheal and bronchial submucosal glands in both normal subjects and those with all stages of lung disease. In contrast to the bronchioles of fetuses and infants without lung pathology, the bronchiolar epithelium of infants with chronic lung disease contained immunostained cells. Immunostained cells were found in areas of migrating dysplastic cells in r

Topics: Acute Disease; Bronchopulmonary Dysplasia; Chronic Disease; Embryonic and Fetal Development; Epidermal Growth Factor; Female; Humans; Hyaline Membrane Disease; Infant, Newborn; Lung Diseases; Male; Middle Aged; Respiratory System; Retrospective Studies

Twelve pairs of fetal lambs were used to test the hypothesis that the necrotizing tracheobronchitis followed by squamous metaplasia seen in premature infants who develop chronic bronchopulmonary dysplasia might be related to low retinol stores and might, therefore, be reversed by retinol supplementation. Epidermal growth factor (EGF) was used to model the growth factor stimulus initiated by chronic wounding of the airways, and retinol was used as a differentiator of proliferating cells stimulated by EGF. Saline-treated animals were used as controls, as were fetal lambs receiving retinol alone or EGF alone. The effects of EGF on tracheal and bronchial epithelium consisted of proliferation of basal and intermediate cells, necrosis and slough of lining ciliated and mucous-producing cells, followed by squamous metaplasia. In fetal lambs given retinol, plasma, liver and lung retinol levels rose and mucous producing cells were increased in number. In the presence of EGF plus retinol, differentiation of mucous-producing cells was accelerated. We believe that this fetal lamb model with low initial levels of retinol in plasma, liver and lung, treated with EGF may mimic human premature infants with chronic bronchopulmonary dysplasia, and that the addition of retinol in amounts sufficient to raise their tissue levels produces a more normal surface epithelium in conducting airways.

Topics: Analysis of Variance; Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Cell Differentiation; Cell Division; Disease Models, Animal; Epidermal Growth Factor; Epithelium; Female; Fetus; Humans; Infant, Newborn; Metaplasia; Microscopy, Electron; Pregnancy; Sheep; Trachea; Vitamin A; Vitamin A Deficiency