Epidermal Growth Factor (EGF)-Like Transforming Growth Factor (TGF) Activity and EGF Receptors in Ovine Fetal Tissues: Possible Role for TGF in Ovine Fetal Development

Freemark, Michael; Comer, Marty

doi:10.1203/00006450-198711000-00026

Cited by 30 publications

(10 citation statements)

References 16 publications

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“…Moreover, fetal tissues have higher levels of EGF-receptor-binding activity than EGF immunoreactivity [28], Thus, it is proposed that .the ligand for the fetal EGF receptor in mice is TGF-a. Similar data have been devel oped for the fetal sheep [34]. Recent information indi cating the presence of TGF in neonatal rat tissues includ ing brain, lung, liver and kidney suggest that TGF-a may be important in neonatal development [35].…”

Section: Egf and Tgf-a In The Fetussupporting

confidence: 65%

Hormone Epidermal Growth Factor Interactions in Development

Fisher

1990

Horm Res

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Epidermal growth factor (EGF) is the most important member of a family of growth factors which exert their effects via a single 170,000 M_r plasma membrane receptor. Other members include transforming growth factor-α (TGF-α), amphiregulin and several viral growth factors. The receptor is widely distributed in fetal and postnatal tissues. The predominant family member in the fetus appears to be TGF-α. EGF production in tissues matures in the perinatal period. Activation of the receptor in the fetal and neonatal periods in rodents evokes important growth and development actions. Tissue EGF and EGF receptor concentrations are modulated by thyroid hormones, estrogen, testosterone and growth hormone, suggesting that selected growth and developmental actions of thyroid and steroid hormones may be mediated by EGF

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Section: Egf and Tgf-a In The Fetussupporting

confidence: 65%

Hormone Epidermal Growth Factor Interactions in Development

Fisher

1990

Horm Res

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“…Data presented here shows that EGF receptor immunoreactivity is present in the developing ovine lung from 51 d gestation onward. A similar ontogeny of EGF-binding sites has been demonstrated in ovine and mouse liver which exhibit EGF-binding sites by midgestation and an increase in EGF receptor before birth (36,38). In the human fetus, bronchial epithelia initially exhibit EGF receptor immunoreactivity near the end of the first trimester; immunoreactivity in bronchial glands appears shortly thereafter (Johnson M, unpublished data).…”

Section: Discussionmentioning

confidence: 74%

“…Recent findings suggest that EGF and TGF-a, another ligand for the EGF receptor, appear during the development of fetal tissues including lung (35)(36)(37), thus raising the possibility that EGF or EGF-like TGFs may influence development of the fetal lung. Fundamental to this hypothesis is the demonstration of the EGF receptor in developing lung tissue in vivo.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of Epidermal Growth Factor Receptor/Kinase and of Lipocortin-1 in the Ovine Lung

et al. 1989

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ABSTRACT. We have examined the ontogeny and distribution of the epidermal growth factor receptorlkinase (EGF receptor) and of lipocortin-1, a major cellular substrate of the EGF receptor, in a developmental series of 13 normal ovine fetal lungs (44-145 d of gestation) using the peroxidase anti-peroxidase technique with two extensively characterized polyclonal antibodies recognizing the EFG receptor and one polyclonal antibody recognizing lipocortin-1. Immunoreactive EGF receptorlkinase and lipocortin-1 were detected in conducting airway epithelium by the end of the first trimester of pregnancy before bronchial glands could be identified. This was followed at two-thirds of gestation by immunoreactivity in bronchial glands and large bronchioles adjacent to postive bronchi. By seveneighths of gestation conducting airway epithelium no longer contained consistently detectable immunostaining for EGF receptor, although lipocortin-1 was identified until term in all levels of conducting airways. In contrast, neither EGF receptor nor lipocortin-1 immunoreactivity was detected in alveolar type I or type I1 epithelial cells, fibrocytes, chondrocytes, smooth muscle, or endothelial cells at any gestational age. These findings suggest that EGF receptor and lipocortin-1 may participate in early airway development. (5), and induces increased thymidine uptake in rat type I1 cells in vitro (6). EGF also enhances synthesis of surfactant associated-protein by type I1 cells (7) and phosphatidylcholine synthesis in fetal rat lung explants (8). These effects are thought to be initiated by growth factor binding to high affinity EGF receptors recently identified in cultured type I1 cells and in fetal rabbit lung homogenates (9); however, the localization of the EGF receptor in intact lung has not been demonstrated.Received September 29, 1988; accepted December 27, 1988. Correspondence and reprint requests: Dr. Mildred Stahlman, Professor of Pediatrics and Pathology, Vanderbilt University, School of Medicine, Nashville, T N 37232.Supported by NIH Grants HL 37726, CA 2407 1, and SCOR HL 14214. Presented in part at the meetings of the American Pediatric Society, Society for Pediatric Research, Washington, DC, May 1988.

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“…Receptors for EGF and its fetal form, transforming growth factor-a, are widely distributed in fetal tissues including the lung and specifically the alveolar type I1 cells (37)(38)(39). This suggests that EGF/transforming growth factor-a plays a role in fetal development.…”

Section: Fie 4 Light Microsco~ic Comparison Of Lung Parenchyma In Rmentioning

confidence: 99%

Prenatal Exposure to Epidermal Growth Factor Attenuates Respiratory Distress Syndrome in Rhesus Infants

et al. 1994

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ABSTRACT. Treatment of nonhuman primate fetuses with epidermal growth factor (EGF) results in histologic and biochemical maturation of their lungs. To determine whether these effects improve lung function postnatally, we studied premature rhesus infants delivered at 78% of gestation after in utero treatment with EGF (n = 5) or placebo ( n = 5). Indices of lung function during the 4 d of postnatal care included fractional concentration of inspired oxygen, peak inspiratory pressure, ventilator rate, mean airway pressure, arterial to alveolar oxygen tension ratio, and ventilation index. Statistically significant differences were noted in the time courses of these variables between EGF-and placebo-treated infants. The direction of the differences indicated that the EGF-treated infants had less severe lung disease. Surfactant apoprotein A concentration and lecithin to sphingomyelin ratio were both significantly higher in the amniotic fluid of the EGF-treated group, indicating advanced biochemical maturation in this group of animals. Whereas birth weight was not affected by EGF exposure, adrenal and gut weights, standardized for body weight, were increased significantly. Histologic studies showed advanced cellular maturation with increased parenchymal airspace and decreased parenchymal tissue space in the EGF-treated group compared with the control group. We conclude that prenatal exposure to EGF stimulates biochemical and histologic maturation of the lung and markedly attenuates the clinical severity of respiratory disease in this model of simian respiratory distress syndrome. (Pediatr Res 35: 30-36, 1994)

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Epidermal Growth Factor (EGF)-Like Transforming Growth Factor (TGF) Activity and EGF Receptors in Ovine Fetal Tissues: Possible Role for TGF in Ovine Fetal Development

Cited by 30 publications

References 16 publications

Hormone Epidermal Growth Factor Interactions in Development

Hormone Epidermal Growth Factor Interactions in Development

Ontogeny of Epidermal Growth Factor Receptor/Kinase and of Lipocortin-1 in the Ovine Lung

Prenatal Exposure to Epidermal Growth Factor Attenuates Respiratory Distress Syndrome in Rhesus Infants

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