ArticleScientific reports2016
The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
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- Sorcin regulates alveolarization and airway tissue remodeling during lung morphogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Calcium-Sensing Receptor as a Novel Target for the Treatment of Idiopathic Pulmonary Fibrosis.Biomolecules · 2025Article
- Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole-Genome Analysis of 7,840 Patients.American journal of respiratory and critical care medicine · 2023Article
- Intraluminal chloride regulates lung branching morphogenesis: involvement of PIEZO1/PIEZO2.Respiratory research · 2023Article
- Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- The role of calcium-sensitive receptor in ovalbumin-induced airway inflammation and hyperresponsiveness in juvenile mice with asthma.The Kaohsiung journal of medical sciences · 2022Article
- Calcium-sensing receptor and CPAP-induced neonatal airway hyperreactivity in mice.Pediatric research · 2022Article
- Negatively charged residues in the membrane ordering activity of SARS-CoV-1 and -2 fusion peptides.Biophysical journal · 2022Article
- Critical Negatively Charged Residues Are Important for the Activity of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides.bioRxiv : the preprint server for biology · 2021Article
- Substratum stiffness tunes membrane voltage in mammary epithelial cells.Journal of cell science · 2021Article
- SARS-CoV-2 Fusion Peptide has a Greater Membrane Perturbating Effect than SARS-CoV with Highly Specific Dependence on CaJournal of molecular biology · 2021Article
- Functional Exploration of the Pulmonary NEB ME.Advances in anatomy, embryology, and cell biology · 2021Article
- Calcium-Sensing Receptor Contributes to Hyperoxia Effects on Human Fetal Airway Smooth Muscle.Frontiers in physiology · 2021Article
- Pulmonary Sensory Receptors.Advances in anatomy, embryology, and cell biology · 2021Article
- Conserved Mechanisms in the Formation of the Airways and Alveoli of the Lung.Frontiers in cell and developmental biology · 2021Article
- Calcium-sensing receptor in the development and treatment of pulmonary hypertension.Molecular biology reports · 2021Review
- Adenylate Cyclase 1 Links Calcium Signaling to CFTR-Dependent Cytosolic Chloride Elevations in Chick Amacrine Cells.Frontiers in cellular neuroscience · 2021Article
- A Developmental Role of the Cystic Fibrosis Transmembrane Conductance Regulator in Cystic Fibrosis Lung Disease Pathogenesis.Frontiers in cell and developmental biology · 2021Review
- Class C GPCRs in the airway.Current opinion in pharmacology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl(-)-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca(2+)-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory diseases.
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