Effects of tracheal occlusion with retinoic acid administration on normal lung development

2017 ◽  
Vol 37 (5) ◽  
pp. 427-434 ◽  
Author(s):  
Amélie Delabaere ◽  
Geoffroy Marceau ◽  
Karen Coste ◽  
Loïc Blanchon ◽  
Pierre-Jean Déchelotte ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Lung Development ◽  
Normal Lung ◽  
Tracheal Occlusion ◽  
Acid Administration

scholarly journals Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

2016 ◽  
Vol 6 (4) ◽  
pp. 407-425 ◽  
Author(s):  
Yuangsheng Gao ◽  
David N. Cornfield ◽  
Kurt R. Stenmark ◽  
Bernard Thébaud ◽  
Steven H. Abman ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Vascular Tone ◽  
Current Knowledge ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Structural Development ◽  
Vasomotor Tone ◽  
Disease States ◽  
Vasculogenesis And Angiogenesis

This review summarizes our current knowledge on lung vasculogenesis and angiogenesis during normal lung development and the regulation of fetal and postnatal pulmonary vascular tone. In comparison to that of the adult, the pulmonary circulation of the fetus and newborn displays many unique characteristics. Moreover, altered development of pulmonary vasculature plays a more prominent role in compromised pulmonary vasoreactivity than in the adult. Clinically, a better understanding of the developmental changes in pulmonary vasculature and vasomotor tone and the mechanisms that are disrupted in disease states can lead to the development of new therapies for lung diseases characterized by impaired alveolar structure and pulmonary hypertension.

scholarly journals The Effects of Postnatal Retinoic Acid Administration on Nephron Endowment in the Preterm Baboon Kidney

2009 ◽  
Vol 65 (4) ◽  
pp. 397-402 ◽  
Author(s):  
Megan R Sutherland ◽  
Lina Gubhaju ◽  
Bradley A Yoder ◽  
Mildred T Stahlman ◽  
M Jane Black
Keyword(s):  
Retinoic Acid ◽  
Nephron Endowment ◽  
Acid Administration

scholarly journals In vitro models of fetal lung development to enhance research into congenital lung diseases

2021 ◽  
Author(s):  
Soichi Shibuya ◽  
Jessica Allen-Hyttinen ◽  
Paolo De Coppi ◽  
Federica Michielin
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Ex Vivo ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
In Vitro Models ◽  
Normal Lung ◽  
Novel Therapeutic Strategies ◽  
Pseudoglandular Stage

Abstract Purpose This paper aims to build upon previous work to definitively establish in vitro models of murine pseudoglandular stage lung development. These can be easily translated to human fetal lung samples to allow the investigation of lung development in physiologic and pathologic conditions. Methods Lungs were harvested from mouse embryos at E12.5 and cultured in three different settings, i.e., whole lung culture, mesenchyme-free epithelium culture, and organoid culture. For the whole lung culture, extracted lungs were embedded in Matrigel and incubated on permeable filters. Separately, distal epithelial tips were isolated by firstly removing mesothelial and mesenchymal cells, and then severing the tips from the airway tubes. These were then cultured either in branch-promoting or self-renewing conditions. Results Cultured whole lungs underwent branching morphogenesis similarly to native lungs. Real-time qPCR analysis demonstrated expression of key genes essential for lung bud formation. The culture condition for epithelial tips was optimized by testing different concentrations of FGF10 and CHIR99021 and evaluating branching formation. The epithelial rudiments in self-renewing conditions formed spherical 3D structures with homogeneous Sox9 expression. Conclusion We report efficient protocols for ex vivo culture systems of pseudoglandular stage mouse embryonic lungs. These models can be applied to human samples and could be useful to paediatric surgeons to investigate normal lung development, understand the pathogenesis of congenital lung diseases, and explore novel therapeutic strategies.

Regulation of retinoic acid signaling during lung morphogenesis

Development ◽  
2000 ◽  
Vol 127 (14) ◽  
pp. 3057-3067 ◽  
Author(s):  
S. Malpel ◽  
C. Mendelsohn ◽  
W.V. Cardoso
Keyword(s):  
Retinoic Acid ◽  
Lung Development ◽  
Branching Morphogenesis ◽  
Initial Stage ◽  
Signaling Center ◽  
Distal Lung ◽  
Immature Lung ◽  
Airway Branching ◽  
Correct Expression

Little is known about how retinoic acid (RA) synthesis, utilization and metabolism are regulated in the embryonic lung and how these activities relate to lung pattern formation. Here we report that early lung bud formation and subsequent branching morphogenesis are characterized by distinct stages of RA signaling. At the onset of lung development RA signaling is ubiquitously activated in primary buds, as shown by expression of the major RA-synthesizing enzyme, RALDH-2 and activation of a RARE-lacZ transgene. Nevertheless, further airway branching appears to require downregulation of RA pathways by decreased synthesis, increased RA degradation in the epithelium via P450RAI-mediated metabolism, and inhibition of RA signaling in the mesenchyme by COUPTF-II expression. These mechanisms controlling local RA signaling may be critical for normal branching, since we show that manipulating RA levels in vitro to maintain RA signaling activated as in the initial stage, leads to an immature lung phenotype characterized by failure to form typical distal buds. We show that this phenotype likely results from RA interfering with the establishment of a distal signaling center, altering levels and distribution of Fgf10 and Bmp4, genes that are essential for distal lung formation. Furthermore, RA upregulates P450RAI expression, suggesting the presence of feedback mechanisms controlling RA availability. Our study illustrates the importance of regional mechanisms that control RA availability and utilization for correct expression of pattern regulators and normal morphogenesis during lung development.

scholarly journals Vitamin A Metabolism by Dendritic Cells Triggers an Antimicrobial Response againstMycobacterium tuberculosis

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Elliot W. Kim ◽  
Avelino De Leon ◽  
Zhichun Jiang ◽  
Roxana A. Radu ◽  
Adrian R. Martineau ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Retinoic Acid ◽  
Immune System ◽  
Vitamin A ◽  
Family Member ◽  
Serum Vitamin ◽  
Normal Lung ◽  
Content Type

ABSTRACTEpidemiological evidence correlates low serum vitamin A (retinol) levels with increased susceptibility to active tuberculosis (TB); however, retinol is biologically inactive and must be converted into its bioactive form, all-transretinoic acid (ATRA). Given that ATRA triggers a Niemann-Pick type C2 (NPC2)-dependent antimicrobial response againstMycobacterium tuberculosis, we investigated the mechanism by which the immune system converts retinol into ATRA at the site of infection. We demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived dendritic cells (DCs), but not macrophages, express enzymes in the vitamin A metabolic pathway, including aldehyde dehydrogenase 1 family, member a2 (ALDH1A2) and short-chain dehydrogenase/reductase family, member 9 (DHRS9), enzymes capable of the two-step conversion of retinol into ATRA, which is subsequently released from the cell. Additionally, mRNA and protein expression levels of ALDH1A2 and DC marker CD1B were lower in tuberculosis lung tissues than in normal lung. The conditioned medium from DCs cultured with retinol stimulated antimicrobial activity fromM. tuberculosis-infected macrophages, as well as the expression of NPC2 in monocytes, which was blocked by specific inhibitors, including retinoic acid receptor inhibitor (RARi) orN,N-diethylaminobenzaldehyde (DEAB), an ALDH1A2 inhibitor. These results indicate that metabolism of vitamin A by DCs transactivates macrophage antimicrobial responses.IMPORTANCETuberculosis (TB) is the leading cause of death by a single infectious agent worldwide. One factor that contributes to the success of the microbe is the deficiency in immunomodulatory nutrients, such as vitamin A (retinol), which are prevalent in areas where TB is endemic. Clinical trials show that restoration of systemic retinol levels in active TB patients is ineffective in mitigating the disease; however, laboratory studies demonstrate that activation of the vitamin A pathway inMycobacterium tuberculosis-infected macrophages triggers an antimicrobial response. Therefore, the goal of this study was to determine the link between host retinol levels and retinoic acid-mediated antimicrobial responses againstM. tuberculosis. By combining establishedin vitromodels within situstudies of lung tissue from TB patients, this study demonstrates that the innate immune system utilizes transcellular metabolism leading to activation between dendritic cells and macrophages as a means to combat the pathogen.

Anti-IL-5 Treatment Attenuates the Asthma Phenotype in Infant Monkeys, but Also Affects Normal Lung Development.

2009 ◽  
Author(s):  
LA Miller ◽  
JE Gerriets ◽  
RO Fishman ◽  
ED Wallis ◽  
KP Maniar ◽  
...  
Keyword(s):  
Lung Development ◽  
Normal Lung ◽  
Asthma Phenotype

scholarly journals Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia

2014 ◽  
Vol 306 (3) ◽  
pp. L246-L259 ◽  
Author(s):  
Thilo J. Witsch ◽  
Paweł Turowski ◽  
Elpidoforos Sakkas ◽  
Gero Niess ◽  
Simone Becker ◽  
...  
Keyword(s):  
Animal Model ◽  
Bronchopulmonary Dysplasia ◽  
Experimental Animal ◽  
Lung Development ◽  
Lung Epithelial Cells ◽  
Experimental Animal Model ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Mrna Levels ◽  
Lysyl Hydroxylase

Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed. All three enzymes were localized to the septal walls in developing mouse lungs, with Plod1 also expressed in the vessel walls of the developing lung and Plod3 expressed uniquely at the base of developing septa. The expression of plod1, plod2, and plod3 was upregulated in the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD. Transforming growth factor (TGF)-β increased plod2 mRNA levels and activated the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts. Using in vivo neutralization of TGF-β signaling in the experimental animal model of BPD, TGF-β was identified as the regulator of aberrant plod2 expression. PLOD2 mRNA expression was also elevated in human neonates who died with BPD or at risk for BPD, compared with neonates matched for gestational age at birth or chronological age at death. These data point to potential roles for lysyl hydroxylases in normal lung development, as well as in perturbed late lung development associated with BPD.

Vitamin D Receptor Deletion Disrupts Normal Lung Development And Leads To An Asthma Phenotype

2011 ◽  
Author(s):  
Virender K. Rehan ◽  
Yishi Li ◽  
Christopher Kovacs ◽  
John S. Torday
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Lung Development ◽  
Normal Lung ◽  
Asthma Phenotype

scholarly journals Chondroitin sulfate proteoglycans are required for lung growth and morphogenesis in vitro

2003 ◽  
Vol 285 (6) ◽  
pp. L1323-L1336 ◽  
Author(s):  
John M. Shannon ◽  
Kathleen McCormick-Shannon ◽  
Michael S. Burhans ◽  
Xiaofei Shangguan ◽  
Kalpana Srivastava ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Lung Development ◽  
Sodium Chlorate ◽  
Surfactant Protein ◽  
Branching Morphogenesis ◽  
Clara Cell ◽  
Normal Lung ◽  
Lung Growth ◽  
Isolated Lung

Proteoglycans (PGs) have been shown to play a key role in the development of many tissues. We have investigated the role of sulfated PGs in early rat lung development by treating cultured tissues with 30 mM sodium chlorate, a global inhibitor of PG sulfation. Chlorate treatment disrupted growth and branching of embryonic day 13 lung explants. Isolated lung epithelium (LgE) migrated toward and invaded lung mesenchyme (LgM), and chlorate irreversibly suppressed this response. Chlorate also inhibited migration of LgE toward beads soaked in FGF10. Chlorate severely decreased branching morphogenesis in tissue recombinants consisting of LgM plus either LgE or tracheal epithelium (TrE) and decreased expression of surfactant protein C gene ( SP-C). Chlorate also reduced bone morphogenetic protein-4 expression in cultured tips and recombinants but had no effect on the expression of clara cell 10-kDa protein ( CC10), sonic hedgehog ( Shh), FGF10, and FGF receptor 2IIIb. Chlorate reduced the growth of LgE in mesenchyme-free culture but did not affect SP-C expression. In contrast, chlorate inhibited both rudiment growth and the induction of SP-C in mesenchyme-free cultured TrE. Treatment of lung tips and tissue recombinants with chondroitinase ABC abolished branching morphogenesis. Chondroitinase also suppressed growth of TrE in mesenchyme-free culture. Chondroitinase treatment, however, had no effect on the induction of SP-C expression in any of these cultures. These results demonstrate the overall importance of sulfated PGs to normal lung development and demonstrate a dynamic role for chondroitin sulfate PGs in embryonic lung growth and morphogenesis.

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