Epidermal growth factor and lung development in the offspring of the diabetic rat
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Epidermal growth factor and lung development in the offspring of the diabetic rat. / Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba; Raaberg, Lasse.
I: Pediatric Pulmonology, Bind 29, Nr. 2, 02.2000, s. 103-12.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Epidermal growth factor and lung development in the offspring of the diabetic rat
AU - Thulesen, J
AU - Poulsen, Steen Seier
AU - Nexø, Ebba
AU - Raaberg, Lasse
N1 - Copyright 2000 Wiley-Liss, Inc.
PY - 2000/2
Y1 - 2000/2
N2 - Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had reduced body weight, but normal lung weight relative to body weight. The air:mesenchyme ratio and the average size of alveoli per mm(2) lung tissue were reduced. The immunoreactivity (IR) of EGF, which was quantified using a computerized image analysis system, appeared with increased intensity and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining against EGF, but decreased the incorporation of thymidine as compared to the results obtained with alveolar cells grown in a normophysiological concentration of glucose (3 mmol/L). Addition of EGF increased the thymidine incorporation only in cells grown in 3 mM glucose. These findings may indicate immaturity of the lungs of pups of untreated diabetic rats, and subtle alterations in the lungs of pups from treated diabetic rats. The results also suggest that glucose plays a role in the expression of EGF, and that cells exposed to high concentrations of glucose are less responsive to EGF.
AB - Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had reduced body weight, but normal lung weight relative to body weight. The air:mesenchyme ratio and the average size of alveoli per mm(2) lung tissue were reduced. The immunoreactivity (IR) of EGF, which was quantified using a computerized image analysis system, appeared with increased intensity and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining against EGF, but decreased the incorporation of thymidine as compared to the results obtained with alveolar cells grown in a normophysiological concentration of glucose (3 mmol/L). Addition of EGF increased the thymidine incorporation only in cells grown in 3 mM glucose. These findings may indicate immaturity of the lungs of pups of untreated diabetic rats, and subtle alterations in the lungs of pups from treated diabetic rats. The results also suggest that glucose plays a role in the expression of EGF, and that cells exposed to high concentrations of glucose are less responsive to EGF.
KW - Animals
KW - Blood Glucose
KW - Cells, Cultured
KW - Culture Media
KW - Diabetes Mellitus, Experimental
KW - Embryonic and Fetal Development
KW - Epidermal Growth Factor
KW - Epithelial Cells
KW - Female
KW - Glucose
KW - Immunohistochemistry
KW - Lung
KW - Organ Size
KW - Proteolipids
KW - Pulmonary Alveoli
KW - Pulmonary Surfactant-Associated Proteins
KW - Pulmonary Surfactants
KW - Rats
KW - Rats, Wistar
KW - Thymidine
M3 - Journal article
C2 - 10639200
VL - 29
SP - 103
EP - 112
JO - Pediatric pulmonology. Supplement
JF - Pediatric pulmonology. Supplement
SN - 1054-187X
IS - 2
ER -
ID: 179058