Control Mechanisms of Lung Alveolar Development and Their Disorders in Bronchopulmonary Dysplasia

Bourbon, Jacques R.; Boucherat, Olivier; Chailley‐Heu, Bernadette; Delacourt, Christophe

doi:10.1203/01.pdr.0000159630.35883.be

Cited by 183 publications

(163 citation statements)

References 127 publications

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“…It consists of a network of proteases/antiproteases including MMP9, MMP12, TIMP1, MMP8, secretory leukocyte peptidase inhibitor, and ADAM metallopeptidase with thrombospondin type 1 motif, 5 (ADAMTS5). The function of MMP9, also called gelatinase B, has been studied in lung development and lung inflammatory diseases such as BPD (3,10). Levels of MMP9 are increased in animal models of BPD (11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

“…The main feature is an arrest of alveolar and capillary formation (2). Models trying to decipher genes involved in the pathophysiology of BPD are mainly based on MV and oxygen application to young mammals with immature lungs of different species (3). In newborn rodent models, analyses of lung structure and gene and protein expression are performed for practical reasons directly at the end of MV (4)(5)(6).…”

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confidence: 99%

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Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

et al. 2015

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Background: Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. Methods: Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. results: In fully treated animals (LPS + MV + 60% O 2 ) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/ wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. conclusion: MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

et al. 2015

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“…Alveolar formation in mouse begins with eruption of secondary crests accompanied by coordinated expression of contractile proteins by interstitial cells (Adler et al, 1989;Jostarndt-Fogen et al, 1998;Yamada et al, 2005) and increased production of elastic matrix (Mariani et al, 2002;RothKleiner and Post, 2005;Foster et al, 2006). Many available mouse genetic models showing severe lung defects in the first postnatal week (Bostrom et al, 1996;Weinstein et al, 1998;Neptune et al, 2003) highlight the importance of the specialized constituents of the lung elastic matrix or the numbers and behavior of interstitial myofibroblasts in secondary septation (reviewed in Bourbon et al, 2005). We, therefore, evaluated these features in mutant lungs by immunostaining for the elastic matrix proteins elastin and fibrillin-1 and for the contractile cell marker SMA (Fig.…”

Section: Mutant Micementioning

confidence: 99%

“…The major defects in lung development seen in ephrinB2 ⌬V/⌬V mice could fit into known requirements for matrix assembly or angiogenesis in alveolar formation. Mouse genetic models showing severe lung defects in the first postnatal week, including mice mutant for platelet-derived growth factor A, fibroblast growth factor receptors 3 and 4, and fibrillin-1 (Bostrom et al, 1996;Weinstein et al, 1998;Neptune et al, 2003) highlight the importance of the specialized constituents of the lung elastic matrix or the numbers and behavior of interstitial myofibroblasts in secondary septation (reviewed in Bourbon et al, 2005). The lung deficiency in ephrinB2 ⌬V/⌬V mice appears to trigger a related mechanical failure in lung development, albeit driven by the vasculature.…”

Section: Other Mouse Models Of Deficient Lung Developmentmentioning

confidence: 99%

Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity

Wilkinson

Schittny

Reinhardt

et al. 2008

Developmental Dynamics

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Alveoli are formed in the lung by the insertion of secondary tissue folds, termed septa, which are subsequently remodeled to form the mature alveolar wall. Secondary septation requires interplay between three cell types: endothelial cells forming capillaries, contractile interstitial myofibroblasts, and epithelial cells. Here, we report that postnatal lung alveolization critically requires ephrinB2, a ligand for Eph receptor tyrosine kinases expressed by the microvasculature. Mice homozygous for the hypomorphic knockin allele ephrinB2 ⌬V/⌬V , encoding mutant ephrinB2 with a disrupted C-terminal PDZ interaction motif, show severe postnatal lung defects including an almost complete absence of lung alveoli and abnormal and disorganized elastic matrix. Lung alveolar formation is not sensitive to loss of ephrinB2 cytoplasmic tyrosine phosphorylation sites. Postnatal day 1 mutant lungs show extracellular matrix alterations without differences in proportions of major distal cell populations. We conclude that lung alveolar formation relies on endothelial ephrinB2 function. Developmental Dynamics 237:2220 -2234, 2008.

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“…4,5 There is growing evidence that not only environmental, but also genetic pressures influence the susceptibility of the preterm infant to BPD. 6,7 Genetic foundations for the development of BPD are implicated in twinning studies, 8,9 which reveal highly significant concordance rates for BPD-almost fourfold in monozygotic, and 1.4-fold in dizygotic twins (P < 0.001). Candidate genes that would place preterm infants at higher risk for developing BPD may involve pathways that mediate responses to infection and inflammation, because a ''cardinal event'' common to many types of chronic lung disease is an inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms of tumor necrosis factor‐α and the susceptibility to bronchopulmonary dysplasia

Strassberg

Cristea

Qian

et al. 2006

Pediatric Pulmonology

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Summary. Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy. A ''New'' BPD has been characterized in preterm infants that may begin in utero, and then progress post-natally, resulting in arrested lung development and alveolar hypoplasia. Foundations for this ''New'' BPD may be derived from pro-inflammatory genes including tumor necrosis factor-a (TNFa). The hypothesis of the current study is that single nucleotide polymorphisms (SNPs) of the pro-inflammatory TNFa gene place preterm infants at increased risk for BPD. Preterm infants (105 in number) with birthweights 1 kg, who survived to at least 36 weeks postmenstrual age (PMA) or discharge were enrolled into this study. They were stratified for BPD according to their need for supplemental oxygen at 28 days and at 36 weeks PMA (non-, mild-, moderate-, or severe-BPD). DNA was extracted from these infants and subjected to analyses for the TNFa SNPs: À1,031, À863, À857, À308, and À238. The PHASE software (version 2.1) was used to reconstruct haplotypes and estimate their frequencies within the study population. Differences in birth weight (P < 0.001) and gestational age (P < 0.001), but not in racial distribution between the groups were found. Haplotype-specific analysis revealed no significant association between BPD severity and any of the 5-marker common haplotypes with 10 or more copies in this study population. Additionally, no significant association was observed in any three SNP haplotypes at À1,031, À863, and À857, and two SNP haplotypes at À308 and À238. We observed no association between BPD severity and the five TNFa SNPs investigated. Pediatr Pulmonol. 2007; 42:29-36. ß

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Control Mechanisms of Lung Alveolar Development and Their Disorders in Bronchopulmonary Dysplasia

Cited by 183 publications

References 127 publications

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity

Single nucleotide polymorphisms of tumor necrosis factor‐α and the susceptibility to bronchopulmonary dysplasia

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