Molecular Regulation of Lung Development

Cardoso, Wellington V.

doi:10.1146/annurev.physiol.63.1.471

Cited by 228 publications

(158 citation statements)

References 128 publications

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“…These findings are similar to those described by Wuenschell et al (30), who found that nicotine stimulated branching and induced the expression of surfactant proteins A and C, suggesting an effect on epithelial cell differentiation and perhaps lung maturation. Of note, the dichotomous and monochotomous branching pattern of nicotine-treated lung explants did not differ from that of untreated explants, suggesting that nicotine may accelerate branching by an early induction of the same cellular processes involved in branching morphogenesis seen in the normal fetal lung such as fibroblast growth factor-10, bone morphogenetic protein-4, and Sonic hedgehog signaling (2).…”

Section: Discussionmentioning

confidence: 90%

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Wongtrakool

Roser‐Page²,

Rivera³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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There is abundant epidemiological data linking prenatal environmental tobacco smoke with childhood asthma and wheezing, but the underlying molecular and physiological mechanisms that occur in utero to explain this link remain unelucidated. Several studies suggest that nicotine, which traverses the placenta, is a causative agent. Therefore, we studied the effects of nicotine on lung branching morphogenesis using embryonic murine lung explants. We found that the expression of α7 nicotinic acetylcholine receptors, which mediate many of the biological effects of nicotine, is highest in pseudoglandular stage lungs compared with lungs at later stages. We then studied the effects of nicotine in the explant model and found that nicotine stimulated lung branching in a dose-dependent fashion. α-Bungarotoxin, an antagonist of α7 nicotinic acetylcholine receptors, blocked the stimulatory effect of nicotine, whereas GTS-21, a specific agonist, stimulated branching, thereby mimicking the effects of nicotine. Explants deficient in α7 nicotinic acetylcholine receptors did not respond to nicotine. Nicotine also stimulated the growth of the explant. Altogether, these studies suggest that nicotine stimulates lung branching morphogenesis through α7 nicotinic acetylcholine receptors and may contribute to dysanaptic lung growth, which in turn may predispose the host to airway disease in the postnatal period.

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Section: Discussionmentioning

confidence: 90%

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Wongtrakool

Roser‐Page²,

Rivera³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Biological processes that transcend stages have long been appreciated. Several novel and canonical biochemical signaling pathways and morphogenic gradients previously associated with the developmental processes of other tissue-organ systems have been implicated in the lung (12)(13)(14)(15).…”

mentioning

confidence: 99%

Transcriptomic Analysis of Human Lung Development

Kho

Bhattacharya

Tantisira

et al. 2010

Am J Respir Crit Care Med

110

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Rationale: Current understanding of the molecular regulation of lung development is limited and derives mostly from animal studies. Objectives: To define global patterns of gene expression during human lung development. Methods: Genome-wide expression profiling was used to measure the developing lung transcriptome in RNA samples derived from 38 normal human lung tissues at 53 to 154 days post conception. Principal component analysis was used to characterize global expression variation and to identify genes and bioontologic attributes contributing to these variations. Individual gene expression patterns were verified by quantitative reverse transcriptase-polymerase chain reaction analysis. Measurements and Main Results: Gene expression analysis identified attributes not previously associated with lung development, such as chemokine-immunologic processes. Lung characteristics attributes (e.g., surfactant function) were observed at an earlier-than-anticipated age. We defined a 3,223 gene developing lung characteristic subtranscriptome capable of describing a majority of the process. In gene expression space, the samples formed a time-contiguous trajectory with transition points correlating with histological stages and suggesting the existence of novel molecular substages. Induction of surfactant gene expression characterized a pseudoglandular ''molecular phase'' transition. Individual gene expression patterns were independently validated. We predicted the age of independent human lung transcriptome profiles with a median absolute error of 5 days, supporting the validity of the data and modeling approach. Conclusions: This study extends our knowledge of key gene expression patterns and bioontologic attributes underlying early human lung developmental processes. The data also suggest the existence of molecular phases of lung development.

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“…The pattern of branching of the lung endoderm is regulated by the surrounding mesenchyme leading to the concept of the epithelial-mesenchymal trophic unit (48)(49)(50).…”

Section: Bronchial Remodeling In Asthmamentioning

confidence: 99%

Epigenetic inheritance of fetal genes in allergic asthma

Bousquet

Jacot

Yssel

et al. 2004

Allergy

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Asthma has been associated with an exaggerated T‐helper type 2 (Th2) over Th1 responses to allergic and nonallergic stimuli, which leads to chronic airway inflammation and airway remodeling. In the present article, we propose that many of the genes involved in IgE synthesis and airways (re)modeling in asthma are persistent or reminiscent fetal genes which may not be silenced during early infancy (or late pregnancy). Genes of the embryologic differentiation of ectodermic and endodermic tissues may explain some of the patterns of airway remodeling in asthma. In utero programming leads to gene expression, the persistence of which may be associated with epigenetic inheritance phenomena induced by nonspecific environmental factors. Clear delineation of these issues may yield new information on the mechanisms of asthma and new targets for therapeutic intervention and primary prevention.

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Molecular Regulation of Lung Development

Cited by 228 publications

References 128 publications

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Transcriptomic Analysis of Human Lung Development

Epigenetic inheritance of fetal genes in allergic asthma

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Molecular Regulation of Lung Development

Cited by 228 publications

References 128 publications

Nicotine alters lung branching morphogenesis through the α7 nicotinic acetylcholine receptor

Nicotine alters lung branching morphogenesis through the α7 nicotinic acetylcholine receptor

Transcriptomic Analysis of Human Lung Development

Epigenetic inheritance of fetal genes in allergic asthma

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Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor