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Results for “Lung development”

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At least 505 records · Page 28Linked to original sources
PubMed2005

Temporal-spatial expression and transcriptional regulation of alpha7 nicotinic acetylcholine receptor by thyroid transcription factor-1 and early growth response factor-1 during murine lung development.

Nicotinic acetylcholine receptors are ligand-gated ion channels formed by five homologous subunits that are involved in processes including signal transduction, proliferation, and apoptosis. The developmental role of these receptors, however, is unclear. In the present investigation, alpha(7) nicotinic acetylcholine receptor expression was assessed by immunohistochemistry in mouse lungs from embryonic day (E)13.5 to postnatal day (PN)20. Transcriptional mechanisms that regulate alpha(7) were assessed by the transfection of murine bronchiolar cells with a reporter containing 1.1 kb of the mouse alpha(7) promoter, TTF-1, and Egr-1. alpha(7) was initially detected at E13.5 in pulmonary mesenchymal cells and in the epithelium of the primitive tubules at E15.5. From E18.5 to PN1, alpha(7) was expressed in conducting airway and saccule epithelial cells. By PN10, expression was observed in the peripheral epithelium and on luminal membranes of bronchiolar epithelial cells in the proximal lung, a pattern that continued through PN20. From E15.5 to PN20, type II alveolar cells expressed both prosurfactant protein C and alpha(7). From E18.5 to PN20, Clara cells in the bronchiolar epithelium co-expressed Clara cell secretory protein and alpha(7). TTF-1 dose-dependently activated alpha(7) transcription in vitro by binding specific TTF-1 regulatory elements in the mouse alpha(7) promoter. Furthermore, alpha(7) was not detected in TTF-1-null mice and markedly increased in TTF-1-overexpressing mice. Conversely, Egr-1 inhibited alpha(7) expression. Temporal-spatial alpha(7) expression supports the concept that these receptors function during normal pulmonary morphogenesis. A model is also supported whereby alpha(7) is induced by the essential pulmonary transcription factor TTF-1 and suppressed by Egr-1 during pulmonary development.

Animals↗
PubMed1987

The effect of maternal CO2 breathing on lung development of fetuses in the rabbit. Morphologic and morphometric studies.

We have examined male fetuses from rabbits exposed from Day 21 to Day 28 of gestation to 8% CO2 for 8 h each day. Fetuses of CO2-exposed mothers weighed less and had lungs that weighed less but when expressed per unit body weight were unchanged. Distended lung volumes were greatly increased in the CO2 group. Light microscope morphometry showed more mature lungs with increased volume proportion of air spaces, decreased air-space wall, and decreased nonparenchyma in CO2-exposed animals. Individual air-spaces were larger, gas exchanging surface area was increased, air-space walls were thinner, and higher ratios of mature to immature crests were found. Electron microscope morphometry showed decreased glycogen in alveolar Type II cells and increased volume proportion of lamellar bodies in the CO2 group. Type II cells were more cuboidal. We interpret these changes to represent increased tissue and cellular maturation in fetuses whose mothers breathed CO2. We speculate that the changes were brought about by increased fetal respiration, which may cause increased stretch and distention of the lung. Alternative mechanisms are discussed.

Animals↗
PubMed2001

Lung development: number of terminal bronchiolar duct endings and gas exchange surface area in victims of sudden infant death syndrome.

Previous research has demonstrated impaired renal development, particularly with respect to glomerular number, in victims of sudden infant death syndrome (SIDS). The present study used stereological principles to estimate the volume of the upper lobe of the right lung, total number of terminal bronchiolar duct endings (TBDE), and gas exchange surface area of this lobe within a group of human infants. The infants were classified according to cause of death (SIDS or non-SIDS), and further subdivided according to birth-weight: normal birth-weight (NBW) or low birth-weight (LBW). The results demonstrated that TBDE density was significantly reduced in SIDS compared to non-SIDS (P = 0.014), but only reduced from non-SIDS NBW values in the SIDS NBW group (P = 0.044). Total TBDE number was significantly reduced in SIDS from non-SIDS (P = 0.001), and was significantly reduced from non-SIDS NBW values in SIDS NBW (P = 0.023). Mean gas exchange surface area per TBDE was significantly increased in SIDS compared to non-SIDS cases (P = 0.049). The results of the present study indicate developmental delay of the lung in SIDS NBW infants who had previously not been considered growth retarded based on their normal body parameters.

Bronchi↗
PubMed2002

Extracellular superoxide dismutase protects lung development in hyperoxia-exposed newborn mice.

We tested the hypothesis that targeted transgenic overexpression of human extracellular superoxide dismutase (EC-SOD) would preserve alveolar development in hyperoxia-exposed newborn mice. We exposed newborn transgenic and wild-type mice to 95% oxygen (O2) or air x 7 days and measured bronchoalveolar lavage cell counts, and lung homogenate EC-SOD, oxidized and reduced glutathione, and myeloperoxidase. We found that total EC-SOD activity in transgenic newborn mice was approximately 2.5x the wild-type activity. Hyperoxia-exposed transgenic mice had less pulmonary neutrophil influx and oxidized glutathione than wild-type littermates at 7 days. We measured alveolar surface and volume density in animals exposed to 14 days more of air or 60% O2. Hyperoxia-exposed transgenic EC-SOD mice had significant preservation of alveolar surface and volume density compared with wild-type littermates. After 7 days 95% O2 + 14 days 60% O2, lung inflammation measured as myeloperoxidase activity was reduced to control levels in all treatment groups.

Animals↗
PubMed2002

Laminin alpha 5 is required for lobar septation and visceral pleural basement membrane formation in the developing mouse lung.

Laminin alpha/beta/gamma heterotrimers are the major noncollagenous components of all basement membranes. To date, five alpha, three beta, and three gamma chains have been identified. Laminin alpha 5 is expressed early in lung development and colocalizes with laminin alpha1. While laminin alpha1 expression in the lung is restricted to the embryonic period, laminin alpha 5 expression persists throughout embryogenesis and adulthood. Targeted mutation of the mouse laminin alpha 5 gene Lama5 causes embryonic lethality at E14-E17 associated with exencephaly, syndactyly, placentopathy, and kidney defects, all attributable to abnormal basement membranes. In this investigation, lung development in Lama5(-/-) mice up to E16.5 was examined. We observed normal lung branching morphogenesis and vasculogenesis, but incomplete lobar septation and absence of the visceral pleura basement membrane. Preservation of branching morphogenesis was associated with ectopic deposition of laminin alpha 4 in the airway basement membrane. Perturbation of pleural basement membrane formation and right lung septation correlated with absence of laminin alpha 5, which was found to be the only laminin alpha chain present in the normal visceral pleura basement membrane. Our finding of normal lung branching morphogenesis with abnormal lobar septation demonstrates that these processes are not obligatorily linked.

Animals↗
PubMed2007

Novel 'phage display antibodies identify distinct heparan sulfate domains in developing mammalian lung.

Heparan sulfate proteoglycans (HSPGs) are essential to respiratory morphogenesis in species as diverse as Drosophila and mice; they play a role in the regulation of numerous HS-binding growth factors, e.g. fibroblast growth factors. Moreover, an HS analogue, heparin, modulates lung growth in vitro. However, it has been difficult to assess the roles of specific HS structures in lung development due to technical barriers to their spatial localisation. Lungs from Sprague-Dawley rats were harvested between E15.5 and E19.5 and immediately fixed in 4 % (w/v) paraformaldehyde (in 0.1 M phosphate-buffered saline (PBS), pH 7.4). Lungs were washed in PBS, cryoprotected with 20% (w/v) sucrose (in PBS), gelatin embedded [7.5% (w/v) gelatin, 15% (w/v) sucrose in PBS], before being covered in Cryo-M-Bed (Bright, Huntingdon, UK) and snap frozen at -40 degrees C. Cryosections were cut at 8 microm and stained with the HSPG core protein specific antibody 3G10 and a HS 'phage display antibody, EW4G2V. 3G10 and EW4G2V immunohistochemistry highlighted the presence of specific HS structures in lungs at all gestational ages examined. 3G10 strongly labelled airway basement membranes and the surrounding mesenchyme and showed weak staining of airway epithelial cells. EW4G2V, however, was far more selective, labelling the airway basement membranes only. Mesenchymal and epithelial cells did not appear to possess the HS epitope recognised by EW4G2V at these gestational ages. Novel 'phage display antibodies allow the spatial distribution of tissue HS to be analysed, and demonstrate in situ that distinct cellular compartments of a tissue possess different HS structures, possibly on the same proteoglycan core protein. These probes offer a new opportunity to determine the role of HS in the pathogenesis of congenital defects such as congenital diaphragmatic hernia (CDH), where lung development is aberrant, and the resulting pulmonary hypoplasia and hypertension are a primary cause of mortality.

Animals↗