TY - JOUR

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 -