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Results for “Lung development”

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At least 451 records · Page 25Linked to original sources
PubMed2003

Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice.

Surfactant Protein C (SP-C) is a secreted transmembrane protein that is exclusively expressed by alveolar type II epithelial cells of the lung. SP-C associates with surfactant lipids to reduce surface tension within the alveolus, maintaining lung volume at end expiration. Mutations in the gene encoding SP-C (SFTPC) have recently been linked to chronic lung disease in children and adults. The goal of this study was to determine whether a disease-linked mutation in SFTPC causes lung disease in transgenic mice. The SFTPC mutation, designated g.1728 G --> A, results in the deletion of exon4, generating a truncated form of SP-C (SP-C(Deltaexon4)). cDNA encoding SP-C(Deltaexon4) was constitutively expressed in type II epithelial cells of transgenic mice. Viable F0 transgene-positive mice were not generated after two separate rounds of pronuclear injections. Histological analysis of lung tissue harvested from embryonic day 17.5 F0 transgene-positive fetuses revealed that SP-C(Deltaexon4) caused a dose-dependent disruption in branching morphogenesis of the lung associated with epithelial cell cytotoxicity. Transient expression of SP-C(Deltaexon4) in isolated type II epithelial cells or HEK293 cells resulted in incomplete processing of the mutant proprotein, a dose-dependent increase in BiP transcription, trapping of the proprotein in the endoplasmic reticulum, and rapid degradation via a proteasome-dependent pathway. Taken together, these data suggest that the g.1728 G --> A mutation causes misfolding of the SP-C proprotein with subsequent induction of the unfolded protein response and endoplasmic reticulum-associated degradation pathways ultimately resulting in disrupted lung morphogenesis.

Animals↗
PubMed1999

Alveolar fluid clearance in developing lungs and its role in neonatal transition.

Successful resuscitation of a fetus and a smooth transition to air breathing is a complex process that requires the orchestration of numerous events. The ability of the newborn to establish adequate ventilation and oxygenation is critically dependent on alveolar expansion and clearing of lung fluid. This transition is aided by changes, including a decrease in lung fluid production, that occur in the immediate period prior to birth. In neonates who face difficulty in establishing air exchange after birth, failure of adequate clearance of lung fluid is an important factor. Such infants are likely to benefit from efforts directed at increasing lung epithelial sodium reabsorption, which in turn will drive water out of the alveolar spaces. We are beginning to understand how these physiologic events occur and some of the factors that can speed up the process. Therapeutic modalities aimed at rescuing infants whose lungs continue to stay flooded are likely to reduce pulmonary morbidity and improve outcome.

Absorption↗
PubMed1986

Lung development and postnatal survival for rats exposed in utero to a high-boiling coal liquid.

Previous studies performed in this laboratory indicated that exposure of rat fetuses to high-boiling coal liquids from 12-14 days of gestation (dg) induced a number of major malformations, including cleft palate, diaphragmatic hernia and small lungs. The study reported here was designed to determine postnatal viability and development of survivors following in utero exposure to Harmarville process solvent (HPS), a wide-boiling-range (150 to greater than 455 degrees C) coal liquid. For this study, 0.74 g kg-1 of the coal liquid was administered (by intragastric intubation) to rats from 12 to 14 dg. Offspring were evaluated for postnatal survival, growth and lung and thymus weights. Randomly selected pups from control and treated litters were killed and necropsied at 1, 3, 7 and 21 days postpartum. In addition, data for control pups were obtained at 0.25 and 0.5 days postpartum for comparison with body, lung and thymus weights of pups that died during this interval. Fifty-four per cent of the exposed pups and 9% of the control pups died between birth and 3 days postpartum. Of the treated pups that died, 10% (6/5; pups/litters) had cleft palate, 27% (17/9) had small lungs and 33% (21/8) had both cleft palate and small lungs. No gross malformations were observed in the remaining 30% of the dead pups. Microscopic examination of lungs from HPS-treated pups revealed no evident histological abnormalities. Body, lung and thymus weights for treated animals that died were significantly less than those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Regulation of the insulin-like growth factor system during normal rat lung development.

Insulin-like growth factor (IGF)-I and IGF-II are small peptide growth factors that interact with a specific membrane receptor, the type 1 IGF receptor, to stimulate cellular proliferation and/or differentiation. The actions of these growth factors and their availability to their receptors are modulated by specific binding proteins, IGF binding protein (IGFBP)-1 through -6, which together with the IGFs and IGF receptors form the IGF system. We have analyzed RNA extracted from fetal (gestation day 16 [E16] through 22 [E22]) and adult (60-day-old) rat lung for expression of each component of the IGF system. IGF-I and -II RNAs are expressed throughout fetal development. IGF-I mRNA remained relatively constant in fetal and adult lung, whereas IGF-II RNA decreased in later gestation to levels below detection by Northern analyses in adult lung. Type 1 IGF receptor expression varied little through all ages studied, whereas the type 2 IGF receptor RNA displayed developmental regulation with a decline in expression with advancing age. IGFBP-1 transcripts were not detected in fetal or adult lung. IGFBP-2 RNA was expressed from E16 to E22, although its abundance decreased in late gestation and in adult lung, with the lowest levels of expression on day E22. IGFBP-3, -4, and -5 had similar profiles of RNA abundance, with fetuses at ages E21 and E22 displaying higher levels of transcript abundance as compared with those aged E17 to E20; the lowest RNA abundance was seen at E20.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Effects of fetal growth restriction on lung development before and after birth: a morphometric analysis.

Our aim was to determine the effects of fetal growth restriction (FGR) during late gestation on the structure of the lungs in the fetus near term and at 8 weeks after birth. The studies were performed using two groups of pregnant sheep and their offspring. In both groups, FGR was induced by umbilico-placental embolisation (UPE); for fetal studies, UPE was performed from 120 days of gestation until 140 days (term, approximately 146 days), when fetuses were killed for tissue analysis. For postnatal studies, UPE continued from 120 days until delivery at term; postnatal lambs were killed at 8 weeks after birth for tissue analysis. UPE led to a thicker pulmonary blood-air barrier at 140 days of gestation and this difference, which was due to a thickened basement membrane, was still present at 8 weeks after birth. At 8 weeks, we also observed a smaller number of alveoli per respiratory unit, thicker interalveolar septa, and a greater volume density of lung tissue in FGR lambs compared to controls. These changes would be expected to impair gas exchange and alter the mechanical properties of the lungs. Our data show that structural alterations in the lungs induced by placental insufficiency were more evident at 8 weeks of postnatal age than near term, indicating that the effects of FGR on the lung may become more serious with age and may affect respiratory health later in life.

Animals↗
PubMed2001

Role of phospholipid transfer protein in rabbit lung development.

A 36-kDa phospholipid transfer protein (PLT-P(R)), which preferentially transfers phosphatidyl choline (PC) compared to phosphatidyl inositol (PI), was purified 827-fold from rabbit lung homogenate. Incorporation of cholesterol in unilamellar vesicles reduced the PC transfer activity of PLTP(R). Dipalmitoyl phosphatidyl choline uptake by alveolar type II cells was increased in the presence of the protein, and further enhanced in the presence of surfactant liposomes. However, a decrease in uptake was noted with cholesterol in host membranes. Incorporation of PI into host membranes had a low stimulatory effect on the process. All these effects were more pronounced in adult type II cells compared to premature, term and 3-day-old pups.

1,2-Dipalmitoylphosphatidylcholine↗