Temporal and spatial regulation of bone morphogenetic protein signaling in late lung development

Alejandre-Alcázar, Miguel A.; Shalamanov, Petar D.; Amarie, Oana V.; Sevilla-Pérez, Julia; Seeger, Werner; Eickelberg, Oliver; Morty, Rory E.

doi:10.1002/dvdy.21293

Cited by 37 publications

(22 citation statements)

References 59 publications

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“…The precise response of cells to Bmps likely depends on the level of ligand, the activity of other signaling pathways, and cell type. Bmps likely play additional roles in later lung development and postnatally (Alejandre-Alcázar et al, 2007). …”

Section: Figurementioning

confidence: 99%

Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development

2010

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The mammalian respiratory system—the trachea and the lungs—arises from the anterior foregut through a sequence of morphogenetic events involving reciprocal endodermal-mesodermal interactions. The lung itself consists of two highly branched, tree-like systems—the airways and the vasculature—that develop in a coordinated way from the primary bud stage to the generation of millions of alveolar gas exchange units. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as branching morphogenesis, vascular development, and the differentiation of multipotent progenitor populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding respiratory disorders, congenital defects in human neonates, and how the disruption of morphogenetic programs early in lung development can lead to deficiencies that persist throughout life.

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Section: Figurementioning

confidence: 99%

Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development

2010

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“…An inhibitor of mTOR, rapamycin, is already used clinically as an immunosuppressant to prevent organ rejection after transplantation [14], [15]. In addition, the use of rapamycin in patients suffering from the destructive lung disease, lymphangioleiomyomatosis [16], has demonstrated promise in its ability to reduce disease symptoms and stabilize lung function [17]. Previously, our lab demonstrated that inhibition of mTOR with rapamycin prevented allergic asthma in a mouse model induced by exposure to the allergen, house dust mite (HDM).…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Rapamycin and Dexamethasone in Mouse Models of Established Allergic Asthma

et al. 2013

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The mammalian target of rapamycin (mTOR) plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM)-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections) and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4–6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR), inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4+ T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4+ T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established.

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“…Multiple studies have demonstrated that platelet derived growth factor (PDGF) and FGF signaling is crucial for myofibroblast differentiation and subsequent onset of secondary septation (24–29). WNT, BMP, and TGFβ signaling components have also been implicated to play a role in fibroblast differentiation during alveolarization (30–32). Additionally, correct deposition of extracellular matrix (ECM) proteins by myofibroblasts, like elastin and collagen, plays a crucial role during secondary septation (33, 34).…”

Section: Introductionmentioning

confidence: 99%

The Future of Bronchopulmonary Dysplasia: Emerging Pathophysiological Concepts and Potential New Avenues of Treatment

Collins¹,

Tibboel²,

Kleer³

et al. 2017

Front. Med.

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Yearly more than 15 million babies are born premature (<37 weeks gestational age), accounting for more than 1 in 10 births worldwide. Lung injury caused by maternal chorioamnionitis or preeclampsia, postnatal ventilation, hyperoxia, or inflammation can lead to the development of bronchopulmonary dysplasia (BPD), one of the most common adverse outcomes in these preterm neonates. BPD patients have an arrest in alveolar and microvascular development and more frequently develop asthma and early-onset emphysema as they age. Understanding how the alveoli develop, and repair, and regenerate after injury is critical for the development of therapies, as unfortunately there is still no cure for BPD. In this review, we aim to provide an overview of emerging new concepts in the understanding of perinatal lung development and injury from a molecular and cellular point of view and how this is paving the way for new therapeutic options to prevent or treat BPD, as well as a reflection on current treatment procedures.

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Temporal and spatial regulation of bone morphogenetic protein signaling in late lung development

Cited by 37 publications

References 59 publications

Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development

Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development

Differential Effects of Rapamycin and Dexamethasone in Mouse Models of Established Allergic Asthma

The Future of Bronchopulmonary Dysplasia: Emerging Pathophysiological Concepts and Potential New Avenues of Treatment

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