ArticleProceedings of the National Academy of Sciences of the United States of America2002
Clara cell impact in air-side activation of CFTR in small pulmonary airways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 60 citations in OpenAlex.
- Loss ofAmerican journal of respiratory cell and molecular biology · 2025Article
- Article
- Unveiling the shared genes between systemic sclerosis and lung cancer.Frontiers in medicine · 2024Article
- Mucins and CFTR: Their Close Relationship.International journal of molecular sciences · 2022Review
- Frontline Science: Pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis.Journal of leukocyte biology · 2018Article
- Transepithelial Fluid and Salt Re-Absorption Regulated by cGK2 Signals.International journal of molecular sciences · 2018Review
- Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Article
- Amiloride-sensitive fluid resorption in NCI-H441 lung epithelia depends on an apical Cl(-) conductance.Physiological reports · 2014Article
- Pendrin, a novel transcriptional target of the uroguanylin system.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2013Review
- Guanylin and functional coupling proteins in the hepatobiliary system of rat and guinea pig.Histochemistry and cell biology · 2012Article
- Can colorectal cancer be prevented or treated by oral hormone replacement therapy?Current molecular pharmacology · 2009Review
- CFTR is activated through stimulation of purinergic P2Y2 receptors.Pflugers Archiv : European journal of physiology · 2009Article
- Respiratory syncytial virus inhibits lung epithelial Na+ channels by up-regulating inducible nitric-oxide synthase.The Journal of biological chemistry · 2009Article
- A Ba2+-resistant, acid-sensitive K+ conductance in Na+-absorbing H441 human airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2007Article
- Cystic fibrosis mice rehabilitated for studies of airway gland dysfunction.The Journal of physiology · 2007Article
- Localization of the iron-regulatory proteins hemojuvelin and transferrin receptor 2 to the basolateral membrane domain of hepatocytes.Histochemistry and cell biology · 2007Article
- Expression of intermediate-conductance, Ca2+-activated K+ channel (KCNN4) in H441 human distal airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2006Article
- C-type natriuretic peptide and its receptor are downregulated in pulmonary epithelium following birth.Histochemistry and cell biology · 2006Article
- Adenosine-evoked Na+ transport in human airway epithelial cells.British journal of pharmacology · 2006Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Clara cells are nonciliated, nonmucous, secretory cells containing characteristic peptidergic granules; they constitute up to 80% of the epithelial cell population of the distal airways. Despite this exposed histotopology and abundance within the terminal airways where fluid secretion is of pivotal importance, the functional role of the Clara cells remained poorly understood. At the transcriptional, translational, and cellular levels, we provide evidence that the Clara cells are well equipped with the bioactive peptide guanylin and proteins of the cGMP-signaling system including guanylate cyclase C, cGMP-dependent protein kinase II, and cystic fibrosis transmembrane conductance regulator (CFTR) together with the two CFTR scaffolding proteins EBP50/NHERF and E3KARP/NHERF-2 that are essential for proper function of CFTR. Guanylin was localized to secretory granules underneath the apical membrane of Clara cells and was, in addition, detected in high concentrations in bronchoalveolar lavage fluid, predicting release of the peptide luminally into the bronchiolar airways. On the other hand, the guanylin-receptor guanylate cyclase C, CFTR, and proteins linked to CFTR activation and function were all confined to the adluminal membrane of Clara cells, implicating an intriguing air-side route of action of guanylin. Whole-cell patch-clamp recordings in the Clara cell line H441 revealed that guanylin activates CFTR Cl(-) conductance via the cGMP but not the cAMP-signaling pathway. Hence, in the critical location of distal airways in situ, the Clara cells may play the outstanding role of CFTR-dependent regulation of epithelial electrolyte/water secretion through a sophisticated paracrine/luminocrine mode of guanylin-induced CFTR activation.
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