Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells

2006 ◽  
Vol 291 (5) ◽  
pp. L950-L956 ◽  
Author(s):  
Jyh-Chang Jean ◽  
Celeste B. Rich ◽  
Martin Joyce-Brady
Keyword(s):  
Hypoxia Inducible Factor ◽  
Fetal Lung ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Developmentally Regulated ◽  
Specific Expression ◽  
Aldolase C ◽  
Expression Studies ◽  
Lung Epithelial ◽  
Responsive Element

Aldolase C (EC 4.1.2.13 ) is a brain-specific aldolase isoform and a putative target of the transcription factor hypoxia-inducible factor (HIF)-1. We identified aldolase C as a candidate hypoxia-regulated gene in mouse lung epithelial (MLE) cells using differential display. We show that the message accumulates in a robust fashion when MLE cells are exposed to 1% oxygen and is inversely related to oxygen content. Induction in hypoxia is dependent on protein synthesis. We localized a hypoxia-responsive element (HRE) in the aldolase C promoter using a series of deletion and heterologous expression studies. The HRE overlaps with a region of the proximal aldolase C promoter that is also related to its brain-specific expression. The HRE contains an Arnt (HIF-1β) and an HIF-1α site. We show that induction in hypoxia is dependent on the HIF-1 site and that HIF-1α protein is present, by gel-shift assay, within nuclear complexes of MLE cells in hypoxia. Aldolase C mRNA expression is developmentally regulated in the fetal lung, rapidly downregulated in the newborn lung at birth, and inducible in the adult lung when exposed to hypoxia. This pattern of regulation is not seen in the brain. This preservation of this HRE in the promoters of four other species suggests that aldolase C may function as a stress-response gene.

Hoxa-5 in mouse developing lung: cell-specific expression and retinoic acid regulation

2000 ◽  
Vol 279 (5) ◽  
pp. L863-L871 ◽  
Author(s):  
Chiwan Kim ◽  
Heber C. Nielsen
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Homeobox Gene ◽  
Fetal Lung ◽  
Lung Epithelial Cells ◽  
Lung Fibroblasts ◽  
Mouse Lung ◽  
Dependent Manner ◽  
Specific Expression ◽  
Protein Expressions

Hoxa-5 is a homeobox gene that is highly expressed in the developing mouse lung. However, little is known about the molecular mechanisms controlling expression. We characterized the ontogeny of Hoxa-5 gene and protein expressions during lung development and then studied the cell-specific effects of retinoic acid (RA) on Hoxa-5 mRNA in fetal lung fibroblasts and MLE-12 mouse lung epithelial cells. Strong but constant Hoxa-5 gene and protein expressions were detected from mouse lung on embryonic day 13.5 to postnatal day 2. At baseline, the gene was strongly expressed in the fibroblasts of day 17.5 fetal mouse lungs. A very weak but reproducible expression was present in the MLE-12 cells. RA stimulated gene expression in both cell types in a time- and dose-dependent manner. Peak expression occurred much later in the MLE-12 cells compared with that in fibroblasts. Cycloheximide and actinomycin D treatment studies suggested that the differences in RA effect on each cell type may involve the presence of a repressor that can be overcome by RA.

scholarly journals Effect of Slit/Robo signaling on regeneration in lung emphysema

2021 ◽  
Author(s):  
Jin-Soo Park ◽  
RyeonJin Cho ◽  
Eun-Young Kang ◽  
Yeon-Mok Oh
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Irreversible Damage ◽  
Lung Epithelial ◽  
And Migration ◽  
Proliferation And Migration

AbstractEmphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema.

scholarly journals Ex vivo model of non‑small cell lung cancer using mouse lung epithelial cells

2017 ◽  
Author(s):  
Taku Sato ◽  
Mami Morita ◽  
Ryota Tanaka ◽  
Yui Inoue ◽  
Miyuki Nomura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Cells ◽  
Small Cell Lung Cancer ◽  
Ex Vivo ◽  
Small Cell ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Small Cell Lung ◽  
Ex Vivo Model ◽  
Lung Epithelial

Mechanotransduction of stretch-induced prostanoid release by fetal lung epithelial cells

2006 ◽  
Vol 291 (3) ◽  
pp. L487-L495 ◽  
Author(s):  
Ian B. Copland ◽  
Denis Reynaud ◽  
Cecil Pace-Asciak ◽  
Martin Post
Keyword(s):  
Mechanical Ventilation ◽  
Arachidonic Acid ◽  
Epithelial Cells ◽  
Fetal Lung ◽  
Lung Epithelial Cells ◽  
Cyclic Stretch ◽  
Mitogen Activated Protein Kinase ◽  
Lung Epithelial ◽  
The Media ◽  
Cox 2

Mechanical ventilation is the primary supportive treatment for infants and adults suffering from severe respiratory failure. Adverse mechanical ventilation (overdistension of the lung) triggers a proinflammatory response. Along with cytokines, inflammatory mediators such as bioactive lipids are involved in the regulation of the inflammatory response. The arachidonic acid pathway is a key source of bioactive lipid mediators, including prostanoids. Although ventilation has been shown to influence the production of prostanoids in the lung, the mechanotransduction pathways are unknown. Herein, we established that cyclic stretch of fetal lung epithelial cells, but not fibroblasts, can evoke an extremely sensitive, rapid alteration in eicosanoid metabolism through a cyclooxygenase (COX)-2 dependent mechanism. Cyclic stretch significantly increased PGI2, PGF2α, PGD2, PGE2, and thromboxane B2 levels in the media of epithelial cells, but did not alter leukotriene B4 or 12-hydroxyeicosatetraenoic acid levels. Inhibition of COX-2, but not COX-1, attenuated the cyclic stretch-induced PG increase in the media, suggesting that cyclic stretch primarily affected PG synthesis. Substrate (free arachidonic acid) availability for PG generation was increased because of a cyclic stretch-induced activation of cytosolic phospholipase A2 (cPLA2) via an influx of extracellular calcium and phosphorylation by mitogen-activated protein kinase, p44/42MAPK. The data are compatible with cPLA2 and COX-2 being intimately involved in regulating the injury response to adverse mechanical ventilation.

Liposome-mediated transfection of fetal lung epithelial cells: DNA degradation and enhanced superoxide toxicity

1998 ◽  
Vol 275 (3) ◽  
pp. L452-L460 ◽  
Author(s):  
A. Keith Tanswell ◽  
Olivier Staub ◽  
Richard Iles ◽  
Rosetta Belcastro ◽  
Judy Cabacungan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Reporter Gene ◽  
Fetal Lung ◽  
Reporter Gene Expression ◽  
Lung Epithelial Cells ◽  
Dna Uptake ◽  
Exogenous Dna ◽  
Lipid Ratio ◽  
Lung Epithelial

Cationic liposomes, 1:1 (mol/mol) 1,2-dioleoyldimethylammonium chloride-1,2-dioleoyl- sn-glycero-3-phosphoethanolamine, were used to transfect primary cultures of distal rat fetal lung epithelial cells with pCMV4-based plasmids. A DNA-to-lipid ratio of 1:10 to 1:15 (wt/wt) optimized DNA uptake over a 24-h exposure. At a fixed DNA-to-lipid ratio of 1:15, chloramphenicol acetyltransferase (CAT) reporter gene expression declined at lipid concentrations > 2.5 nmol/cm2 cell surface area, whereas DNA uptake remained concentration dependent. CAT expression peaked 48 h after removal of the liposome-DNA complex, declining thereafter. Reporter gene expression was increased, and supercoiled cDNA degradation was reduced by the addition of 0.2 mM nicotinamide and 10 μM chloroquine. Rat fetal lung epithelial cells transfected with two different expression cassettes had an increased susceptibility to superoxide-mediated cytotoxicity. This could be attributed to a nonspecific delivery of exogenous DNA or some other copurified factor. The DNA-dependent increase in superoxide-mediated cytotoxicity, but not basal levels of cytotoxicity, was inhibited by the addition of 0.2 mM nicotinamide and 10 μM chloroquine.

scholarly journals Selection of rhinovirus 1A variants adapted for growth in mouse lung epithelial cells

Virology ◽  
2011 ◽  
Vol 420 (2) ◽  
pp. 82-88 ◽  
Author(s):  
Angela L. Rasmussen ◽  
Vincent R. Racaniello
Keyword(s):  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Lung Epithelial ◽  
Selection Of
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