scholarly journals N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung DevelopmentIn VivoandIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Zhengchang Liao ◽  
Xiaocheng Zhou ◽  
Ziqiang Luo ◽  
Huiyi Huo ◽  
Mingjie Wang ◽  
...  
Keyword(s):  
Lung Development ◽  
Fetal Lung ◽  
Lung Weight ◽  
Mk 801 ◽  
Fetal Lung Development ◽  
Fetal Rat ◽  
Intrauterine Hypoxia ◽  
Excessive Activation

Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs) are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR’s expression and role in fetal lung development.Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E) 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801’s influence on intrauterine hypoxia-induced retardation of fetal lung development was testedin vivo, and NMDA’s direct effect on fetal lung development was observed using fetal lung organ culturein vitro.Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damagein vivo.In vitroexperiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression.Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

scholarly journals Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow mesenchymal stem cells on promoting alveolarization in bronchopulmonary dysplasia

2019 ◽  
Vol 316 (6) ◽  
pp. C815-C827 ◽  
Author(s):  
Yinyan Yue ◽  
Ziqiang Luo ◽  
Zhengchang Liao ◽  
Liming Zhang ◽  
Shuai Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lung Development ◽  
Bone Marrow Mscs ◽  
Mk 801 ◽  
Intrauterine Hypoxia ◽  
Marrow Mesenchymal Stem Cells ◽  
Cell Cycling ◽  
Excessive Activation

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.

Glucocorticoids upregulate tropoelastin expression during late stages of fetal lung development

1995 ◽  
Vol 268 (3) ◽  
pp. L491-L500 ◽  
Author(s):  
R. A. Pierce ◽  
W. I. Mariencheck ◽  
S. Sandefur ◽  
E. C. Crouch ◽  
W. C. Parks
Keyword(s):  
Lung Development ◽  
Matrix Protein ◽  
Fetal Lung ◽  
Extracellular Matrix Protein ◽  
Transferase Activity ◽  
Mrna Levels ◽  
Pregnant Rats ◽  
Fetal Lung Development ◽  
Chloramphenicol Acetyl Transferase Activity

The production of elastin, an essential extracellular matrix protein of terminal airway interstitium, occurs mostly during early development. Because glucocorticoids influence airway maturation, we studied the effect of dexamethasone (Dex) on tropoelastin expression during fetal lung development. Timed-pregnant rats were treated with Dex (1 mg/kg daily), and fetal lungs were collected 3 days later at 17, 19, and 21 days of gestation. Dex treatment resulted in about a threefold increase in tropoelastin mRNA levels at 19 days concomitant with accelerated airway development. By in situ hybridization, Dex treatment increased the number of tropoelastin-expressing cells and the level of tropoelastin mRNA per cell. In organ culture, Dex increased lung tropoelastin expression and augmented cortisol stimulation of tropoelastin expression. In fetal pulmonary artery smooth muscle cells, 10(-8) M Dex upregulated tropoelastin mRNA expression and increased tropoelastin promoter-chloramphenicol acetyl transferase activity in transient transfections. These data indicate that pharmacologically administered glucocorticoids transcriptionally upregulate fetal lung tropoelastin expression and suggest that steroid hormones may be important regulators of elastin production in vivo.

ROCK2 is involved in accelerated fetal lung development induced by in vivo lung distension

2010 ◽  
Vol 45 (10) ◽  
pp. 966-976 ◽  
Author(s):  
Marc Cloutier ◽  
Monique Tremblay ◽  
Bruno Piedboeuf
Keyword(s):  
Lung Development ◽  
Fetal Lung ◽  
Fetal Lung Development

Rabbit surfactant protein C: cDNA cloning and regulation of alternatively spliced surfactant protein C mRNAs

1992 ◽  
Vol 263 (6) ◽  
pp. L634-L644 ◽  
Author(s):  
V. Boggaram ◽  
R. K. Margana
Keyword(s):  
Gene Expression ◽  
Lung Development ◽  
Genomic Dna ◽  
Protein C ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein C ◽  
Fetal Lung Development ◽  
Mrna Content

Surfactant protein C (SP-C), a hydrophobic protein of pulmonary surfactant is essential for surfactant function. Toward elucidating molecular mechanisms that mediate regulation of SP-C gene expression in rabbit lung, we isolated and characterized cDNAs encoding rabbit SP-C and studied the regulation of SP-C gene expression during fetal lung development and by adenosine 3',5'-cyclic monophosphate (cAMP) and dexamethasone in fetal lung tissues in vitro. We found that rabbit SP-C is highly homologous to SP-C of other species and is encoded by two mRNAs that differ by an insertion of 31 nucleotides in the 3' untranslated regions. SP-C mRNAs were classified into two types based on the nucleotide sequence; type I represents RNA without the 31 nucleotide insert and comprises approximately 80–90% of total SP-C mRNA content, whereas type II represents RNA containing the insert and comprises approximately 10–20% of total SP-C mRNA content. SP-C mRNAs were induced in a coordinate manner during fetal lung development and by cAMP and dexamethasone in fetal lung tissues in vitro. Southern hybridization analysis of genomic DNA suggested that SP-C mRNAs are encoded by a single gene. Polymerase [corrected] chain reaction-amplification of genomic DNA with oligonucleotide primers flanking the insertional sequence and sequence analysis of amplified DNA showed that SP-C mRNAs are produced by alternative use of 3' splice sites of intron 5 of SP-C gene.

FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in myofibroblasts

2005 ◽  
Vol 288 (1) ◽  
pp. L43-L51 ◽  
Author(s):  
Bernadette Chailley-Heu ◽  
Olivier Boucherat ◽  
Anne-Marie Barlier-Mur ◽  
Jacques R. Bourbon
Keyword(s):  
Lung Development ◽  
Lysyl Oxidase ◽  
Smooth Muscle Actin ◽  
Fold Increase ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Fetal Fibroblasts

The fibroblast growth factors (FGFs) are key players in fetal lung development, but little is known about their status in postnatal lung. Here, we investigated the expression pattern of FGF-18 transcripts through the perinatal period and evidenced a sevenfold increase after birth that paralleled changes in elastin expression. In vitro, recombinant human (rh)FGF-18 had a mitogenic activity on day 21 fetal rat lung fibroblasts and stimulated its own expression in the latter, whereas FGF-2 inhibited it. At 50 or 100 ng/ml, rhFGF-18 increased the expression of α-smooth muscle actin (α-SMA; 2.5-fold), a characteristic marker of myofibroblasts, of tropoelastin (6.5-fold), of lysyl oxidase (2-fold), and of fibulins 1 and 5 (8- and 2.2-fold) in confluent fibroblasts isolated from fetal day 21 lung; similar results were obtained with fibroblasts from day 3 postnatal lungs. Elastin protein expression was also slightly increased in fetal fibroblasts. Lung analysis on day 4 in rat pups that had received rhFGF-18 (3 μg) on days 0 and 1 showed a 1.7-fold increase of tropoelastin transcripts, whereas α-SMA transcripts were unchanged. In contrast, rhFGF-2 markedly decreased expression of elastin in vitro and in vivo and of fibulin 5 in vitro. In addition, vitamin A, which is known to enhance alveolar development, elevated FGF-18 and elastin expressions in day 2 lungs, thus advancing the biological increase. We postulate that FGF-18 is involved in postnatal lung development through stimulating myofibroblast proliferation and differentiation.

Localization of Epidermal Growth Factor Receptor in Alveolar Epithelium During Human Fetal Lung Development in Vitro

1995 ◽  
Vol 21 (6) ◽  
pp. 917-939 ◽  
Author(s):  
Jonathan M. Klein ◽  
Blayne L. Fritz ◽  
Troy A. McCarthy ◽  
Christine L. Wohlford-Lenane ◽  
Jeanne M. Snyder
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Lung Development ◽  
Growth Factor Receptor ◽  
Alveolar Epithelium ◽  
Fetal Lung ◽  
Fetal Lung Development ◽  
Epidermal Growth ◽  
Development In Vitro ◽  
Human Fetal Lung

Mesenchymal determination of mechanical strain-induced fetal lung cell proliferation

1998 ◽  
Vol 275 (3) ◽  
pp. L545-L550 ◽  
Author(s):  
Jing Xu ◽  
Mingyao Liu ◽  
A. Keith Tanswell ◽  
Martin Post
Keyword(s):  
Epithelial Cells ◽  
Dna Synthesis ◽  
Lung Development ◽  
Mechanical Strain ◽  
Fetal Lung ◽  
Cell Types ◽  
Fetal Lung Development ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Fetal Breathing Movements

Fetal breathing movements play an important role in normal fetal lung growth. We have previously shown that an intermittent mechanical strain regimen (60 cycles/min, 15 min/h), simulating normal fetal breathing movements, stimulated growth of mixed fetal rat lung cells in organotypic culture. In the present study, we examined the individual responses of the two major fetal lung cell types, fibroblasts and epithelial cells, to mechanical strain. Also, we investigated the effect of mesenchymal-epithelial interactions on strain-induced cell proliferation during fetal lung development. Fibroblasts and epithelial cells from day 18to day 21 fetal rat lung (term = 22 days), cultured alone or as various recombinants, were subjected to either a 48-h static culture or to strain, and DNA synthesis was measured. Both cell types responded individually to strain with enhanced DNA synthesis throughout late fetal lung development. Independent of the recombination ratio, there was no additive response to strain when fibroblasts and epithelial cells from the same gestation were recombined. In contrast, strain-induced DNA synthesis was suppressed when cells from different gestations were recombined. The ontogenic response pattern of recombinants to mechanical strain was similar to that of fibroblasts but not of epithelial cells. Strain-induced proliferation increased and peaked at the early canalicular stage of lung development at 19 days of gestation and declined thereafter. We conclude that strain-enhanced growth of the fetal lung is gestation dependent and that the gestational response to mechanical force is regulated by the mesenchyme.

Transcription and mRNA stability regulate developmental and hormonal expression of rabbit surfactant protein B gene

1995 ◽  
Vol 268 (3) ◽  
pp. L481-L490 ◽  
Author(s):  
R. K. Margana ◽  
V. Boggaram
Keyword(s):  
Gene Transcription ◽  
Mrna Stability ◽  
Lung Development ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Mrna Levels ◽  
Fetal Lung Development ◽  
Surfactant Protein B ◽  
Protein B

Surfactant protein B (SP-B), a hydrophobic protein of pulmonary surfactant, is essential for the surface tension-reducing properties of surfactant. In the present study, we isolated and characterized cDNAs encoding rabbit SP-B, and used transcription run-on assays and Northern blot analysis to investigate the role of transcriptional and posttranscriptional mechanisms in the developmental and cAMP and dexamethasone induction of SP-B mRNA. We found two forms of SP-B cDNAs that differed by an insertion of 69 nucleotides in the 3' untranslated regions. We found that transcription across the SP-B gene is nonequimolar and the 3' end of the gene has high levels of antisense transcription. SP-B gene transcription and SP-B mRNA levels increased during fetal lung development. However, increased SP-B mRNA levels could not be accounted for primarily on the basis of increased transcription. These results suggested that enhanced SP-B gene transcription and enhanced SP-B mRNA stability mediate developmental induction of SP-B gene. In rabbit fetal lung in vitro, both dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) and dexamethasone increased SP-B mRNA levels. DBcAMP-dependent increase in SP-B mRNA levels resulted from increased SP-B gene transcription, whereas dexamethasone-dependent increase resulted from combined effects on increased SP-B gene transcription and SP-B mRNA stability. In tissues treated with dexamethasone the half-life (t1/2) of SP-B mRNA increased > 2.5-fold (t1/2 control = 9 h; t1/2 dex-treated = 25 h). These data show that both transcription and mRNA stability regulate induction of SP-B gene expression during fetal lung development and by cAMP and dexamethasone in fetal lung in vitro.

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