Pulmonary neuroendocrine cells and lung development

1996 ◽  
Vol 7 (3) ◽  
pp. 173-201 ◽  
Author(s):  
Mary E. Sunday
Keyword(s):  
Lung Development ◽  
Neuroendocrine Cells ◽  
Pulmonary Neuroendocrine Cells

scholarly journals Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development

2006 ◽  
Vol 290 (1) ◽  
pp. L185-L193 ◽  
Author(s):  
Jie Pan ◽  
Ian Copland ◽  
Martin Post ◽  
Herman Yeger ◽  
Ernest Cutz
Keyword(s):  
Lung Development ◽  
Tryptophan Hydroxylase ◽  
Mechanical Strain ◽  
Fetal Lung ◽  
Mechanical Stretch ◽  
Serotonin Release ◽  
Neuroendocrine Cells ◽  
Cyclic Stretch ◽  
Mechanosensitive Channels ◽  
Pulmonary Neuroendocrine Cells

Pulmonary neuroendocrine cells (PNEC) produce amine (serotonin, 5-HT) and peptides (e.g., bombesin, calcitonin) with growth factor-like properties and are thought to play an important role in lung development. Because physical forces are essential for lung growth and development, we investigated the effects of mechanical strain on 5-HT release in PNEC freshly isolated from rabbit fetal lung and in the PNEC-related tumor H727 cell line. Cultures exposed to sinusoidal cyclic stretch showed a significant 5-HT release inhibitable with gadolinium chloride (10 nM), a blocker of mechanosensitive channels. In contrast to hypoxia (Po2 ∼ 20 mmHg), stretch-induced 5-HT release was not affected by Ca2+-free medium or nifedipine (50 μM), excluding the exocytic pathway. In H727 cells, stretch failed to release calcitonin, a peptide stored within dense core vesicles (DCV), whereas hypoxia caused massive calcitonin release. 5-HT released by mechanical stretch is derived predominantly from the cytoplasmic pool, because it is rapid (∼5 min) and is releasable from early (20 days of gestation) fetal PNEC containing few DCV. Both mechanical stretch and hypoxia upregulated expression of tryptophan hydroxylase, the rate-limiting enzyme of 5-HT synthesis. We conclude that mechanical strain is an important physiological stimulus for the release of 5-HT from PNEC via mechanosensitive channels with potential effects on lung development and resorption of lung fluid at the time of birth.

scholarly journals Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ling Cai ◽  
Hongyu Liu ◽  
Fang Huang ◽  
Junya Fujimoto ◽  
Luc Girard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Neuroendocrine Cells ◽  
Immune Gene ◽  
Small Cell Lung ◽  
Immune Gene Expression ◽  
Pulmonary Neuroendocrine Cells

AbstractSmall cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.

scholarly journals Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia

2022 ◽  
Author(s):  
Kasra Khalaj ◽  
Rebeca Lopes Figueira ◽  
Lina Antounians ◽  
Sree Gandhi ◽  
Matthew Wales ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Congenital Diaphragmatic Hernia ◽  
Extracellular Vesicles ◽  
Diaphragmatic Hernia ◽  
Lung Development ◽  
Pulmonary Hypoplasia ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
Neuroendocrine Cells ◽  
Beta Catenin

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, beta-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages, and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.

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