Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

Aguayo, S M; Schuyler, WE; Murtagh, James J.; Roman, Jesse

doi:10.1165/ajrcmb.10.6.8003340

Cited by 64 publications

(33 citation statements)

References 25 publications

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“…In the mouse, Sunday et al and King et al (28,29) have demonstrated that bombesin can stimulate DNA and saturated phosphatidylcholine (SPC) synthesis in fetal lung. Similarly, Aguayo et al (30) have also demonstrated that bombesin can stimulate airway branching in mouse lung explants. However, it is noteworthy that the GRP is expressed relatively later in gestation in mice than in humans (17,28), and that in contrast to humans, GRP immunoreactivity cannot be localized to mouse PNEC (31 ).…”

mentioning

confidence: 81%

A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth.

Li¹,

Nagalla²,

Spindel³

1994

J. Clin. Invest.

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Gastrin-releasing peptide (GRP) is developmentally expressed in human fetal lung and is a growth factor for normal and neoplastic lung but its role in normal lung development has yet to be clearly defined. In this study we have characterized the expression of GRP and its receptor in fetal rhesus monkey lung and determined the effects of bombesin on fetal lung development in vitro. By RNA blot analysis, GRP mRNA was first detectable in fetal monkey lung at 63 days gestation, reached highest levels at 80 days gestation, and then declined to near adult levels by 120 days gestation; a pattern closely paralleling GRP expression in human fetal lung. As in human lung, in situ hybridization localized GRP mRNA to neuroendocrine cells though during the canalicular phase of development (between 63-80 days gestation) GRP mRNA was present not only in classic pulmonary neuroendocrine cells, but also in cells of budding airways. Immunohistochemistry showed that bombesin-like immunoreactivity was present in neuroendocrine cells, but not in budding airways, suggesting that in budding airways either the GRP mRNA is not translated, is rapidly secreted, or a related, but different RNA is present. RNase protection analysis using a probe to the monkey GRP receptor demonstrated that the time course of receptor RNA expression closely paralleled the time course of GRP RNA expression. In situ hybridization showed that GRP receptors were primarily expressed in epithelial cells of the developing airways. Thus GRP would appear to be secreted from neuroendocrine cells to act on target cells in developing airways. This hypothesis was confirmed by organ culture of fetal monkey lung in the presence of bombesin and bombesin antagonists. Bombesin treatment at 1 and 10 nM significantly increased DNA synthesis in airway epithelial cells and significantly increased the number and size of airways in cultured fetal lung. In fact, culturing 60 d fetal lung for 5 d with 10 nM bombesin increased airway size and number nearly to that observed in cultured 80 d fetal lung. The effects of bombesin could be blocked by specific GRP receptor antagonists. Thus

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mentioning

confidence: 81%

A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth.

Li¹,

Nagalla²,

Spindel³

1994

J. Clin. Invest.

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“…The murine lung explant model has been previously described (1). Briefly, timed pregnant CD57BL/6J mice were killed to obtain embryos at embryonic day 11(E11).…”

Section: Animalsmentioning

confidence: 99%

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Wongtrakool

Roser‐Page²,

Rivera³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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There is abundant epidemiological data linking prenatal environmental tobacco smoke with childhood asthma and wheezing, but the underlying molecular and physiological mechanisms that occur in utero to explain this link remain unelucidated. Several studies suggest that nicotine, which traverses the placenta, is a causative agent. Therefore, we studied the effects of nicotine on lung branching morphogenesis using embryonic murine lung explants. We found that the expression of α7 nicotinic acetylcholine receptors, which mediate many of the biological effects of nicotine, is highest in pseudoglandular stage lungs compared with lungs at later stages. We then studied the effects of nicotine in the explant model and found that nicotine stimulated lung branching in a dose-dependent fashion. α-Bungarotoxin, an antagonist of α7 nicotinic acetylcholine receptors, blocked the stimulatory effect of nicotine, whereas GTS-21, a specific agonist, stimulated branching, thereby mimicking the effects of nicotine. Explants deficient in α7 nicotinic acetylcholine receptors did not respond to nicotine. Nicotine also stimulated the growth of the explant. Altogether, these studies suggest that nicotine stimulates lung branching morphogenesis through α7 nicotinic acetylcholine receptors and may contribute to dysanaptic lung growth, which in turn may predispose the host to airway disease in the postnatal period.

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“…Its encoding gene is on chromosome 3, and it has a molecular weight of 98,000, is characterized by a neutral optimum pH, and is a plasma membrane-bound metalloproteinase (17). Many peptides have been found to be substrates for NEP, for example, enkephalin (20,21), substance P (22), bombesinlike peptide (16,23), endothelin (24,25), bradykinin (22) and others (26). The other name for NEP, enkephalinase, reflects the fact that NEP can degrade enkephalin in association with nerves (21,27,28).…”

Section: Discussionmentioning

confidence: 99%

Neprilysin Is Identical to Skin Fibroblast Elastase

Morisaki

Moriwaki

Sugiyama-Nakagiri

et al. 2010

Journal of Biological Chemistry

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Although human skin fibroblast (HSF) elastase has been characterized as a membrane-bound metalloproteinase, little is known about its structure, amino acid sequence, and encoding gene. As there are similarities in the molecular weights and inhibitory profiles of HSF elastase and neprilysin (neutral endopeptidase 24.11 (NEP)), in this study we tested the hypothesis that they are identical using immunoprecipitation and transfection methods. An immunoprecipitation study demonstrated that HSF elastase activity co-immunoprecipitated with anti-NEP in lysates of cultured HSF. Transfection of an NEP cDNA expression vector into COS-1 cells elicited the expression of HSF elastase and NEP activities in the transfected cells. These findings strongly suggest that HSF elastase is identical to NEP, which functions mainly in neuron-associated cells to degrade neuropeptides. Analysis of the expression pattern of NEP revealed that its expression was remarkably up-regulated at the gene, protein, and enzymatic activity levels during the replicative senescence of cultured HSF. Further, the activity of NEP was markedly enhanced in a pattern similar to elastase activity during the intrinsic aging of mouse skin, in UVA-exposed HSF as well as in HSF treated with conditioned medium from UVBexposed human keratinocytes. Analysis of the cytokine profile for the stimulation of NEP and HSF elastase activities in HSF demonstrated that among the 11 cytokines tested, IL-1␣, IL-1␤, IL-6, IL-8, and GM-CSF had the potential to significantly stimulate both activities similarly, again supporting the identity of HSF elastase and NEP.Cumulative exposure to sunlight elicits the formation of wrinkles, which are associated with marked decreases in skin elasticity (1-3). We demonstrated previously that skin elasticity is remarkably diminished in an early phase of long term UV irradiation at a dose of less than 1 minimal erythemal dose (MED), which is accompanied by degeneration of the elastic fiber network (consisting of premature oxytalan, elaunin fibers, and mature elastic fibers) (1, 2). We also reported that elastase activity is gradually and markedly increased in the wrinkling process prior to the onset of wrinkle formation in UVB-exposed hairless mouse skin (4), which suggests the deep involvement of elastases in the damage of the elastic fiber network. The evidence that the exposure of animal skin to UVB at less than a suberythemal dose can cause wrinkles, despite the lack of inflammatory cell infiltration (5), led us to speculate that skin fibroblast elastase is mainly responsible for the degradation of elastic fibers. While characterizing the elastase-like enzyme derived from skin fibroblasts, we found that fibroblast elastase, which exhibits the characteristics of a metalloproteinase, is remarkably inhibited by metalloproteinase inhibitors but not by other inhibitors, which indicates that the fibroblast elastase belongs to the metalloproteinase family. To determine the contribution of fibroblast elastase activity to the deterioration of elastins ...

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Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

Cited by 64 publications

References 25 publications

A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth.

A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth.

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Neprilysin Is Identical to Skin Fibroblast Elastase

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Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

Cited by 64 publications

References 25 publications

A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth.

A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth.

Nicotine alters lung branching morphogenesis through the α7 nicotinic acetylcholine receptor

Neprilysin Is Identical to Skin Fibroblast Elastase

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Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor