scholarly journals The Role of Ephrins-B1 and -B2 During Fetal Rat Lung Development

2015 ◽  
Vol 35 (1) ◽  
pp. 104-115 ◽  
Author(s):  
Francisca O. Peixoto ◽  
Patrícia Pereira-Terra ◽  
Rute S. Moura ◽  
Emanuel Carvalho-Dias ◽  
Jorge Correia-Pinto ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Lung Development ◽  
Fetal Lung ◽  
Cardiovascular Development ◽  
Rat Lung ◽  
Growth Promoters ◽  
Lung Morphogenesis ◽  
Rat Lungs ◽  
Fetal Rat

Background/ Aims: The knowledge of the molecular network that governs fetal lung branching is an essential step towards the discovery of novel therapeutic targets against pulmonary pathologies. Lung consists of two highly branched systems: airways and vasculature. Ephrins and its receptors, Eph, have been implicated in cardiovascular development, angiogenesis and vascular remodeling. This study aims to clarify the role of these factors during lung morphogenesis. Methods: Ephrins-B1, -B2 and receptor EphB4 expression pattern was assessed in fetal rat lungs between 15.5 and 21.5 days post-conception, by immunohistochemistry. Fetal rat lungs were harvested at 13.5 dpc, cultured during 4 days and treated with increasing doses of ephrins-B1 and -B2 and the activity of key signaling pathways was assessed. Results: Ephrin-B1 presents mesenchymal expression, whereas ephrin-B2 and its receptor EphB4 were expressed by the epithelium. Both ephrins stimulated pulmonary branching. Moreover, while ephrin-B1 did not affect the pathways studied, ephrin-B2 supplementation decreased activity of JNK, ERK and STAT. This study characterizes the expression pattern of ephrins-B1, -B2 and EphB4 receptor throughout rat lung development. Conclusion: Our data highlight a possible role of ephrins as molecular stimulators of lung morphogenesis. Moreover, it supports the idea that classical vascular factors might play a role as airway growth promoters.

Growth and developmental regulation of wnt-2 (irp) gene in mesenchymal cells of fetal lung

1992 ◽  
Vol 262 (6) ◽  
pp. L672-L683 ◽  
Author(s):  
B. K. Levay-Young ◽  
M. Navre
Keyword(s):  
Lung Development ◽  
Developmental Regulation ◽  
Fetal Lung ◽  
Fibroblast Cell ◽  
Mrna Levels ◽  
Rat Lung ◽  
Intercellular Interaction ◽  
Wnt Proteins ◽  
Fetal Rat ◽  
Fetal Rat Lung

The wnt gene family encodes a group of proteins implicated as intercellular signaling molecules in vertebrate development. Because many wnt genes are also expressed in the lung, we have examined whether the wnt family member wnt-2 (irp) plays a role in lung development. We have cloned rat wnt-2 and found that this cDNA detects multiple mRNAs expressed at high levels in fetal rat lung. Much lower levels were found in adult rat lung and other tissues, including, surprisingly, the mammary gland. The wnt-2 mRNA was also detected in human fetal lung fibroblast cell lines, where the mRNA levels were dramatically regulated by growth state as well as growth factor stimulation. In situ hybridization showed that, in fetal rat lung, wnt-2 mRNA expression is restricted to the mesenchyme; levels in the developing epithelium were indistinguishable from background. Based on the known properties of other wnt proteins, our data lead us to propose that wnt-2 may play a role in lung development by mediating intercellular interaction(s) between mesenchyme and epithelium.

scholarly journals The Role of Glycoprotein 130 Family of Cytokines in Fetal Rat Lung Development

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67607 ◽  
Author(s):  
Cristina Nogueira-Silva ◽  
Paulina Piairo ◽  
Emanuel Carvalho-Dias ◽  
Carla Veiga ◽  
Rute S. Moura ◽  
...  
Keyword(s):  
Lung Development ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

Sex hormones regulate CFTR in developing fetal rat lung epithelial cells

1997 ◽  
Vol 272 (5) ◽  
pp. L844-L851 ◽  
Author(s):  
N. B. Sweezey ◽  
F. Ghibu ◽  
S. Gagnon
Keyword(s):  
Epithelial Cells ◽  
Sex Hormones ◽  
Functional Activity ◽  
Lung Development ◽  
Fetal Lung ◽  
Lung Epithelial Cells ◽  
Rat Lung ◽  
Fetal Rat ◽  
Lung Epithelial ◽  
Fetal Rat Lung

Sex hormones modulate two normal processes of late-gestation mammalian lung development: the onset of augmented production of surfactant phospholipids and the loss of mesenchymal cells. As prenatal lung development advances, epithelial chloride secretory pathways diminish as opposing sodium absorptive pathways increase in expression. We hypothesized that sex hormones may influence both the gene expression and functional activity of the chloride channel known as the cystic fibrosis transmembrane conductance regulator (CFTR) in fetal lung epithelium. We report here that sex hormones exert opposite effects on CFTR. Androgen increases and estrogen decreases CFTR functional activity [as assessed by CFTR antisense (but not sense) oligodeoxynucleotide-sensitive adenosine 3',5'-cyclic monophosphate-stimulated cell volume reduction or by glibenclamide-sensitive, amiloride-insensitive transepithelial electrical potential] in primary cultures of fetal rat lung epithelial cells. No alterations in CFTR mRNA levels measured by quantitative polymerase chain reaction amplification of reverse transcripts) accompanied either the changes in functional activity induced by sex hormones or the changes observed during normal development, suggesting that sex hormone modulation of CFTR in antenatal lung occurs at a posttranscriptional level. Our data are consistent with the hypothesis that both androgen and estrogen contribute to the male disadvantage with respect to fetal lung functional development.

Glucocorticoid receptor mRNA and protein in fetal rat lung in vivo: modulation by glucocorticoid and androgen

1998 ◽  
Vol 275 (1) ◽  
pp. L103-L109 ◽  
Author(s):  
Neil B. Sweezey ◽  
F. Ghibu ◽  
S. Gagnon ◽  
E. Schotman ◽  
Q. Hamid
Keyword(s):  
Glucocorticoid Receptor ◽  
Primary Culture ◽  
Lung Development ◽  
Fetal Lung ◽  
Lung Cells ◽  
Human Antibody ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

Pulmonary glucocorticoid receptor (GR) is essential to timely preparation for the onset of breathing air at birth. We have previously used primary culture of late-gestation fetal rat lung cells to demonstrate differential regulation of GR by glucocorticoid depending on cell type. In this study, we hypothesized that the action of glucocorticoid on GR mRNA expression and protein elaboration in lung cells might be modulated by interactions present in vivo but not in primary culture. Given that male sex hormone (androgen) has an inhibitory effect on antenatal lung development, we also postulated that androgen would decrease antenatal lung GR. We report that antenatal maternal injection of the glucocorticoid dexamethasone (1 mg/kg) enhanced fetal lung cellular levels of GR mRNA and protein as assessed by in situ hybridization and immunocytochemistry (ICC), respectively. ICC was performed using polyclonal rabbit anti-human antibody that reacts with rat GR whether bound to ligand or not and does not interfere with GR binding to DNA. Levels of GR mRNA and protein were enhanced in cells throughout all areas of the lung tissue, suggesting that interactions occurring in intact tissue may override the previously reported direct inhibition by glucocorticoid of GR protein elaboration in isolated fetal rat lung epithelial cells. Furthermore, antenatal administration of the androgen 5α-dihydrotestosterone (0.2 mg/kg) reduced tissue levels of GR mRNA and protein, consistent with androgenic inhibition of antenatal lung development by decreasing GR. We conclude that glucocorticoids and androgens exert opposite effects on fetal lung GR.

scholarly journals MicroRNA-127 modulates fetal lung development

2009 ◽  
Vol 37 (3) ◽  
pp. 268-278 ◽  
Author(s):  
Manoj Bhaskaran ◽  
Yang Wang ◽  
Honghao Zhang ◽  
Tingting Weng ◽  
Pradyumna Baviskar ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Lung Development ◽  
Fetal Lung ◽  
Mirna Microarray ◽  
Mirna Expression Pattern ◽  
Opposite Trend ◽  
Fetal Lung Development ◽  
Terminal Bud ◽  
Lung Organ Culture

MicroRNAs (miRNAs) are small endogenous RNAs and are widely regarded as one of the most important regulators of gene expression in both plants and animals. To define the roles of miRNAs in fetal lung development, we profiled the miRNA expression pattern during lung development with a miRNA microarray. We identified 21 miRNAs that showed significant changes in expression during lung development. These miRNAs were grouped into four distinct clusters based on their expression pattern. Cluster 1 contained miRNAs whose expression increased as development progressed, while clusters 2 and 3 showed the opposite trend of expression. miRNAs in cluster 4 including miRNA-127 (miR-127) had the highest expression at the late stage of fetal lung development. Quantitative real-time PCR validated the microarray results of six selected miRNAs. In situ hybridization demonstrated that miR-127 expression gradually shifted from mesenchymal cells to epithelial cells as development progressed. Overexpression of miR-127 in fetal lung organ culture significantly decreased the terminal bud count, increased terminal and internal bud sizes, and caused unevenness in bud sizes, indicating improper development. These findings suggest that miR-127 may have an important role in fetal lung development.

Protein phosphatase inhibitors arrest cell cycle and reduce branching morphogenesis in fetal rat lung cultures

2000 ◽  
Vol 278 (5) ◽  
pp. L1062-L1070 ◽  
Author(s):  
B. Keith Taylor ◽  
Tamara D. Stoops ◽  
Allen D. Everett
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Branching Morphogenesis ◽  
Rat Lung ◽  
Lung Growth ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Epithelial Marker ◽  
Airway Branching

Protein phosphatase 2A (PP2A) is a key signal transduction intermediate in the regulation of cellular proliferation and differentiation in vitro. However, the role of PP2A in the context of a developing organ is unknown. To explore the role of PP2A in the regulation of lung development, we studied the effect of PP2A inhibition on new airway branching, induction of apoptosis, DNA synthesis, and expression of epithelial marker genes in whole organ explant cultures of embryonic (E14) rat lung. Microdissected lung primordia were cultured in medium containing one of either two PP2A inhibitors, okadaic acid (OA, 0–9 nM) or cantharidin (Can, 0–3,600 nM), or with the PP2B inhibitor deltamethrin (Del, 0–10 μM) as a control for a PP2A-specific effect for 48 h. PP2A inhibition with OA and Can significantly inhibited airway branching and overall lung growth. PP2B inhibition with Del did not affect lung growth or new airway development. Histologically, both PP2A- and PP2B-inhibited explants were similar to controls. Increased apoptosis was not the mechanism of decreased lung growth and new airway branching inasmuch as OA-treated explant sections subjected to the terminal deoxynucleotidyltransferase dUTP nick end labeling reaction demonstrated a decrease in apoptosis. However, PP2A inhibition with OA increased DNA content and 5-bromo-2′-deoxyuridine uptake that correlated with a G2/M cell cycle arrest. PP2A inhibition also resulted in altered differentiation of the respiratory epithelium as evidenced by decreased mRNA levels of the early epithelial marker surfactant protein C. These findings suggest that inhibition of protein phosphatases with OA and Can halted mesenchymal cell cycle progression and reduced branching morphogenesis in fetal rat lung explant culture.

Lysosomal-type PLA2and turnover of alveolar DPPC

2001 ◽  
Vol 280 (4) ◽  
pp. L748-L754 ◽  
Author(s):  
Aron B. Fisher ◽  
Chandra Dodia
Keyword(s):  
Degradation Products ◽  
Specific Inhibitor ◽  
Rat Lung ◽  
Lamellar Bodies ◽  
Lung Uptake ◽  
Rat Lungs ◽  
Choline Incorporation ◽  
Total Tissue ◽  
Intact Rats

This study evaluated the role of a lysosomal-type phospholipase A2(aiPLA2) in the degradation of internalized dipalmitoylphosphatidylcholine (DPPC) and in phospholipid synthesis by the rat lung. Uptake and degradation of DPPC were measured in isolated perfused rat lungs over 3 h following endotracheal instillation of [3H]DPPC in mixed unilamellar liposomes plus or minus MJ33, a specific inhibitor of lung aiPLA2. Uptake of DPPC was calculated from total tissue-associated radiolabel, and degradation was calculated from the sum of radiolabel in degradation products. Both uptake and degradation were markedly stimulated by addition of 8-bromo-cAMP to the perfusate. MJ33 had no effect on DPPC uptake but decreased DPPC degradation at 3 h by ∼40–50%. The effect of MJ33 on lung synthesis of DPPC was evaluated with intact rats over a 12- to 24-h period following intravenous injection of radiolabeled palmitate and choline. MJ33 treatment decreased palmitate incorporation into disaturated phosphatidylcholine of lamellar bodies and surfactant by ∼65% at 24 h but had no effect on choline incorporation. This result is compatible with inhibition of the deacylation/reacylation pathway for DPPC synthesis. These results obtained with intact rat lungs indicate that aiPLA2is a major enzyme for degradation of internalized DPPC and also has an important role in DPPC synthesis.

scholarly journals Influence of Epidermal Growth Factor on Fetal Rat Lung Development in Vitro

1986 ◽  
Vol 20 (5) ◽  
pp. 473-477 ◽  
Author(s):  
Lan Gross ◽  
Diane W Dynia ◽  
Seamus A Rooney ◽  
Douglas A Smart ◽  
Joseph B Warshaw ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Lung Development ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Epidermal Growth ◽  
Development In Vitro
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