Bronchial ligation enhances murine fetal lung development in whole-organ culture

Blewett, Christopher; Zgleszewski, Steven E.; Chinoy, Mala R.; Krummel, Thomas M.; Cilley, Robert E.

doi:10.1016/s0022-3468(96)90400-5

Cited by 50 publications

(29 citation statements)

References 14 publications

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“…Lungs from control and Sham fetuses were fixed at a distending pressure of 10 cmH 2 O to obtain uniform inflation. There are no data for tracheal pressure in fetal rats after TO, but other investigators have reported that tracheal pressure increases by ϳ4 cmH 2 O in fetal sheep with TO (38) and after bronchial ligation in whole organ culture of mouse lungs (7). Thus it is likely that, in the present study, the control and Sham lungs were fixed at a higher distending pressure than the TO lungs.…”

Section: Discussionmentioning

confidence: 66%

Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Yoshizawa

Chapin

Sbragia

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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. Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats. Am J Physiol Lung Cell Mol Physiol 285: L344-L353, 2003. First published April 4, 2003 10.1152/ajplung.00281.2002 has been reported to stimulate lung growth but decreases number and maturation of type II cells, effects that vary with gestational age and duration of TO. We examined effects of a novel method of TO (unipolar microcautery to seal the trachea) produced at 19.5-20 days (d) of gestation in fetal rats; fetuses were delivered at term, 22 d. Controls were sham operated and unoperated littermates. TO increased wet lung weight but not dry lung weight or lung DNA and protein. To evaluate further the effects of TO, we examined the cell cycle regulators, cyclins D1 and A, in fetal lungs. Cyclin D1 increased with TO (P Ͻ 0.005). TO also increased expression of the type I epithelial cell marker RTI40 (mRNA and protein). TO decreased mRNA for surfactant proteins (SP)-A and -C but did not affect protein levels of SP-A and -B and of RTII70, a type II epithelial cell marker. We conclude that TO by microcautery, even of short duration, has diverse pulmonary effects including stimulating increased levels of cyclin D1 with probable cell cycle progression, type I cell differentiation, and possibly inhibiting type II cell function.cyclins; fetal lung development; lung growth; pulmonary epithelial differentiation; pulmonary surfactant LATE IN GESTATION, the fetal lung rapidly changes in appearance from an almost glandular tissue into a lacy, thin-walled organ capable of efficient gas exchange and surfactant production. During this period lung growth, septal thinning, maturation of the surfactant system, and differentiation of alveolar type I and type II cells occur. Normal fetal lung development is crucial for survival in extrauterine life, but factors that control these developmental processes and their interdependence have been incompletely defined.Lung growth and maturation of the surfactant system are the most widely studied aspects of late fetal lung development. Fetal lung growth is dependent on several mechanical factors, including adequate intrathoracic space, sufficient amniotic fluid volume, normal fetal breathing movements, and a positive transpulmonary distending pressure (21,27). In contrast, maturation of the surfactant system is highly dependent on endocrine factors (4, 50). There is relatively little information about factors that are responsible for differentiation of alveolar epithelial type I and type II cells in vivo.Several investigators have shown that occlusion of the trachea in experimental animals increases lung growth but has adverse affects on type II cell number and function (2,10,11,15,40). These changes occur when tracheal occlusion (TO) is produced relatively early in gestation and maintained for a prolonged period. In contrast, when TO is produced later in gestation for a relatively short period, lung growth is stimulated, and adverse affects on the type II cell population are di...

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Section: Discussionmentioning

confidence: 66%

Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Yoshizawa

Chapin

Sbragia

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Total protein content from normal and nitrofen-exposed lungs was determined by Bio-Rad protein microassay (3,4,6). Thirty-microgram aliquots of total protein for VEGF and Flk-1 detection and 40-g aliquots of total protein for ANG-1 from normal and hypoplastic lungs at different developmental stages were separated by SDS-PAGE (12,6, and 10% gels, respectively) and electroblotted to a polyvinylidene difluoride membrane (Millipore, Bedford, MA), employing the methods published earlier (6).…”

Section: Methodsmentioning

confidence: 99%

Angiopoietin-1 and VEGF in vascular development and angiogenesis in hypoplastic lungs

Chinoy¹,

Graybill²,

Miller³

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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We hypothesized that exposure of murine fetuses to environmental toxins, such as nitrofen, during early embryogenesis alters vasculogenesis. To address our hypothesis, we assessed protein levels of endothelial cell-selective angiogenic factors: angiopoietin (ANG)-1, vascular endothelial growth factor (VEGF), and mediator of VEGF signaling, VEGF receptor-2 [fetal liver kinase (Flk)-1], a transmembrane receptor tyrosine kinase. VEGF and Flk-1 proteins were lower in hypoplastic lungs from pseudoglandular to alveolar stages than in normal lungs at equivalent developmental time points significant for induction of pulmonary vasculogenesis and angiogenesis. ANG-1 protein was higher in hypoplastic lungs than in normal lungs at all the developmental stages considered in this study, i.e., pseudoglandular, canalicular, saccular, and alveolar stages. We assessed exogenous VEGF-mediated endothelial cell response on extracellular signal-regulated kinase (ERK) 1/2, also referred to as p44/42 mitogen-activated protein kinase. Hypoplastic lungs had more elevated ERK 1/2 protein than normal developing lungs. Exposure to exogenous VEGF activated ERK 1/2 in normal developing lungs but not in hypoplastic lungs. Our results suggest that in hypoplastic lungs: 1) low VEGF signifies negative effects on vasculogenesis/angiogenesis and indicates altered endothelial-mesenchymal interactions; 2) increased ANG-1 protein may be required to maintain vessel integrity and quiescence; and 3) regulation of ERK 1/2 protein is affected in hypoplastic lungs. We speculate that extensive remodeling of blood vessels in hypoplastic lungs may occur to compensate for structurally and functionally defective vasculature.

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“…Certainly, physical force can modulate the rate of branching, inasmuch as tracheal ligation, which doubles the intraluminal pressure in embryonic lung, significantly accelerates branching (153). However, the numerous null mutants now available show that growth factors such as FGF10 and SHH are essential and these null mutations can abrogate the influence of increased force.…”

Section: Molecular Origin Of the Epithelial Tip-splitting Eventmentioning

confidence: 99%

Molecular Mechanisms of Early Lung Specification and Branching Morphogenesis

et al. 2005

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Bronchial ligation enhances murine fetal lung development in whole-organ culture

Cited by 50 publications

References 14 publications

Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Angiopoietin-1 and VEGF in vascular development and angiogenesis in hypoplastic lungs

Molecular Mechanisms of Early Lung Specification and Branching Morphogenesis

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