ArticleThe Journal of physiology2008
Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- 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
- Intraluminal chloride regulates lung branching morphogenesis: involvement of PIEZO1/PIEZO2.Respiratory research · 2023Article
- Stereo-Specific Modulation of the Extracellular Calcium-Sensing Receptor in Colon Cancer Cells.International journal of molecular sciences · 2021Article
- Functional Exploration of the Pulmonary NEB ME.Advances in anatomy, embryology, and cell biology · 2021Article
- Pulmonary Sensory Receptors.Advances in anatomy, embryology, and cell biology · 2021Article
- Upregulation of airway smooth muscle calcium-sensing receptor by low-molecular-weight hyaluronan.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.Nature reviews. Endocrinology · 2018Review
- Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Article
- The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR.Scientific reports · 2016Article
- The extracellular calcium-sensing receptor, CaSR, in fetal development.Best practice & research. Clinical endocrinology & metabolism · 2013Review
- Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP(3) pathway and the ryanodine receptor.American journal of physiology. Renal physiology · 2013Article
- Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels.PloS one · 2013Article
- Comparative molecular developmental aspects of the mammalian- and the avian lungs, and the insectan tracheal system by branching morphogenesis: recent advances and future directions.Frontiers in zoology · 2012Article
- Enhanced Ca(2+)-sensing receptor function in idiopathic pulmonary arterial hypertension.Circulation research · 2012Article
- Allosteric modulation of the calcium-sensing receptor by gamma-glutamyl peptides: inhibition of PTH secretion, suppression of intracellular cAMP levels, and a common mechanism of action with L-amino acids.The Journal of biological chemistry · 2011Article
- Lung organogenesis.Current topics in developmental biology · 2010Review
- Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR.Pflugers Archiv : European journal of physiology · 2009Review
- The extracellular Ca2+-sensing receptor branches out--a new role in lung morphogenesis.The Journal of physiology · 2008Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Postnatal lung function is critically dependent upon optimal embryonic lung development. As the free ionized plasma calcium concentration ([Ca(2+)](o)) of the fetus is higher than that of the adult, the process of lung development occurs in a hypercalcaemic environment. In the adult, [Ca(2+)](o) is monitored by the G-protein coupled, extracellular calcium-sensing receptor (CaR), but neither its ontogeny nor its potential role in lung development are known. Here, we demonstrate that CaR is expressed in the mouse lung epithelium, and that its expression is developmentally regulated, with a peak of expression at embryonic day 12.5 (E12.5) and a subsequent decrease by E18, after which the receptor is absent. Experiments carried out using the lung explant culture model in vitro show that lung branching morphogenesis is sensitive to [Ca(2+)](o), being maximal at physiological adult [Ca(2+)](o) (i.e. 1.0-1.3 mM) and lowest at the higher, fetal (i.e. 1.7 mM) [Ca(2+)](o). Administration of the specific CaR positive allosteric modulator, the calcimimetic R-568, mimics the suppressive effects of high [Ca(2+)](o) on branching morphogenesis while both phospholipase C and PI3 kinase inhibition reverse these effects. CaR activation suppresses cell proliferation while it enhances intracellular calcium signalling, lung distension and fluid secretion. Conditions which are restrictive either to branching or to secretion can be rescued by manipulating [Ca(2+)](o) in the culture medium. In conclusion, fetal Ca(2+)(o), acting through a developmentally regulated CaR, is an important extrinsic factor that modulates the intrinsic lung developmental programme. Our observations support a novel role for the CaR in preventing hyperplastic lung disease in utero.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.