Peristalsis of airway smooth muscle is developmentally regulated and uncoupled from hypoplastic lung growth

Jesudason, Edwin C.; Smith, Nicola; Connell, M.Gwen; Spiller, David G.; White, Mike; Fernig, David G.; Losty, Paul D.

doi:10.1152/ajplung.00498.2005

Cited by 49 publications

(47 citation statements)

References 36 publications

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“…Such spontaneous peristaltic Ca 2ϩ waves and contractions appear to be coupled and arise from specific "pacemaker"-like ASM cells and intercellular communications via gap junctions (71,136). Although the mechanisms underlying these waves are still under investigation, membrane potential, L-type Ca 2ϩ channels, and chloride currents appear to play a role (which makes the developing ASM different from the adult).…”

Section: Airway Developmentmentioning

confidence: 99%

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Prakash

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

177

154

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Prakash YS. Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol 305: L912-L933, 2013. First published October 18, 2013 doi:10.1152/ajplung.00259.2013.-It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca 2ϩ ]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro-vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM "activity" result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis.

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Section: Airway Developmentmentioning

confidence: 99%

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Prakash

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

177

154

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“…Fibroblast growth factor-10 expression is crucial for fine tuning the spatiotemporal ASMC activity early in human development. The relationship between lung hypoplasia, fibroblast growth factor-10 deficiency, and dysfunctional ASMC from birth onward is linked (28), and as a perturbation of this relationship by nitrofen results in abnormal smooth muscle relaxation near term. Calponin (CNN1), a multifunctional orthologous protein in both rats and humans in ASMC, is tightly restricted to differentiated ASMC lineages including those in the lung during embryonic and postnatal life.…”

Section: Mirnas Regulate Nitrofen-induced Airway Smooth Muscle Cell Dmentioning

confidence: 99%

The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia

Mahood

Johar

et al. 2015

Pediatr Res

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Background:We currently do not know how the herbicide nitrofen induces lung hypoplasia and congenital diaphragmatic hernia in rats. Our aim was to compare the differentially expressed transcriptome of nitrofen-induced hypoplastic lungs to control lungs in embryonic day 13 rat embryos before the development of embryonic diaphragmatic defects. Methods: Using next-generation sequencing technology, we identified the expression profile of microRNA (miRNA) and mRNA genes. Once the dataset was validated by both RT-qPCR and digital-PCR, we conducted gene ontology, miRNA target analysis, and orthologous miRNA sequence matching for the deregulated miRNAs in silico. results: Our study identified 186 known mRNA and 100 miRNAs which were differentially expressed in nitrofeninduced hypoplastic lungs. Sixty-four rat miRNAs homologous to known human miRNAs were identified. A subset of these genes may promote lung hypoplasia in rat and/or human, and we discuss their associations. Potential miRNA pathways relevant to nitrofen-induced lung hypoplasia include PI3K, TGF-β, and cell cycle kinases. conclusion: Nitrofen-induced hypoplastic lungs have an abnormal transcriptome that may lead to impaired development.

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“…In an effort to explain the association of diaphragmatic and extradiaphragmatic defects, the mesenchymal hit hypothesis has been proposed (17,(32)(33)(34). This hypothesis posits that: 1) similar signaling pathways are involved in the differentiation of mesenchymal cells in all of the affected organs; and 2) the function of mesenchymal cells in the affected organs is disrupted by genetic or environmental triggers.…”

Section: Gene Mutations That Impair Mesenchymal Cell Functionmentioning

confidence: 99%

Molecular genetics of congenital diaphragmatic defects

et al. 2007

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Congenital diaphragmatic hernia (CDH) is a severe birth defect that is accompanied by malformations of the lung, heart, testis, and other organs. Patients with CDH may have any combination of these extradiaphragmatic defects, suggesting that CDH is often a manifestation of a global embryopathy. This review highlights recent advances in human and mouse genetics that have led to the identification of genes involved in CDH. These include genes for transcription factors, molecules involved in cell migration, and extracellular matrix components. The expression patterns of these genes in the developing embryo suggest that mesenchymal cell function is compromised in the diaphragm and other affected organs in patients with CDH. We discuss potential mechanisms underlying the seemingly random combination of diaphragmatic, pulmonary, cardiovascular, and gonadal defects in these patients.

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Peristalsis of airway smooth muscle is developmentally regulated and uncoupled from hypoplastic lung growth

Abstract: of airway smooth muscle is developmentally regulated and uncoupled from hypoplastic lung growth.

Cited by 49 publications

References 36 publications

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia

Molecular genetics of congenital diaphragmatic defects

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