ArticleProceedings of the National Academy of Sciences of the United States of America2009
Diminished sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- A molecular systems architecture of asthma.Frontiers in immunology · 2026Pooled it
- UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids.Cell death & disease · 2026Article
- Mechanically induced dysregulation of calcium homeostasis: a molecular linchpin in asthmatic pathogenesis.European journal of medical research · 2025Review
- Sorcin regulates alveolarization and airway tissue remodeling during lung morphogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- Bronchomotor tone imbalance evokes airway hyperresponsiveness.Expert review of respiratory medicine · 2024Review
- Impact of obesity on airway remodeling in asthma: pathophysiological insights and clinical implications.Frontiers in allergy · 2024Review
- New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis.Clinical science (London, England : 1979) · 2023Review
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Co-Expression Analysis of Airway Epithelial Transcriptome in Asthma Patients with Eosinophilic vs. Non-Eosinophilic Airway Infiltration.International journal of molecular sciences · 2023Article
- Airway Smooth Muscle Regulated by Oxidative Stress in COPD.Antioxidants (Basel, Switzerland) · 2023Review
- Airway smooth muscle in contractility and remodeling of asthma: potential drug target mechanisms.Expert opinion on therapeutic targets · 2023Article
- Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation.Nature communications · 2022Article
- Bronchial smooth muscle cell in asthma: where does it fit?BMJ open respiratory research · 2022Review
- Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction.Minerva medica · 2022Article
- Role of airway smooth muscle cell phenotypes in airway tone and obstruction in guinea pig asthma model.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2022Article
- STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum CaFrontiers in immunology · 2022Article
- Airway smooth muscle function in asthma.Frontiers in physiology · 2022Review
- Adiponectin and Asthma: Knowns, Unknowns and Controversies.International journal of molecular sciences · 2021Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Phenotypic modulation of airway smooth muscle (ASM) is an important feature of airway remodeling in asthma that is characterized by enhanced proliferation and secretion of pro-inflammatory chemokines. These activities are regulated by the concentration of free Ca(2+) in the cytosol ([Ca(2+)](i)). A rise in [Ca(2+)](i) is normalized by rapid reuptake of Ca(2+) into sarcoplasmic reticulum (SR) stores by the sarco/endoplasmic reticulum Ca(2+) (SERCA) pump. We examined whether increased proliferative and secretory responses of ASM from asthmatics result from reduced SERCA expression. ASM cells were cultured from subjects with and without asthma. SERCA expression was evaluated by western blot, immunohistochemistry and real-time PCR. Changes in [Ca(2+)](i), cell spreading, cellular proliferation, and eotaxin-1 release were measured. Compared with control cells from healthy subjects, SERCA2 mRNA and protein expression was reduced in ASM cells from subjects with moderately severe asthma. SERCA2 expression was similarly reduced in ASM in vivo in subjects with moderate/severe asthma. Rises in [Ca(2+)](i) following cell surface receptor-induced SR activation, or inhibition of SERCA-mediated Ca(2+) re-uptake, were attenuated in ASM cells from asthmatics. Likewise, the return to baseline of [Ca](i) after stimulation by bradykinin was delayed by approximately 50% in ASM cells from asthmatics. siRNA-mediated knockdown of SERCA2 in ASM from healthy subjects increased cell spreading, eotaxin-1 release and proliferation. Our findings implicate a deficiency in SERCA2 in ASM in asthma that contributes to its secretory and hyperproliferative phenotype in asthma, and which may play a key role in mechanisms of airway remodeling.
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Registered trials
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.