ArticleThe Journal of clinical investigation2020
Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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
32 citing papers in PubMed, 52 citations in OpenAlex.
- Altered Degranulation and pH of Neutrophil Phagosomes Impacts Antimicrobial Efficiency in Cystic Fibrosis.Frontiers in immunology · 2020Trial
- Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Inflammation and epithelial-mesenchymal transition in a CFTR-depleted human bronchial epithelial cell line revealed by proteomics and human organ-on-a-chip.The FEBS journal · 2025Article
- Association between inflammatory proteins and rotator cuff tears: a bidirectional Mendelian randomization study.Scientific reports · 2025Article
- Innate Immunity in Cystic Fibrosis: Varied Effects of CFTR Modulator Therapy on Cell-to-Cell Communication.International journal of molecular sciences · 2025Review
- Loss of neutrophil Shp1 produces hemorrhagic and lethal acute lung injury.bioRxiv : the preprint server for biology · 2024Article
- Review
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Optimizing anesthesia and delivery approaches for dosing into lungs of mice.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Cystic fibrosis transmembrane conductance regulator modulators attenuate platelet activation and aggregation in blood of healthy donors and COVID-19 patients.The European respiratory journal · 2023Article
- Multimodal analysis of granulocytes, monocytes, and platelets in patients with cystic fibrosis before and after Elexacaftor-Tezacaftor-Ivacaftor treatment.Frontiers in immunology · 2023Article
- The Impact of Highly Effective Modulator Therapy on Cystic Fibrosis Microbiology and Inflammation.Clinics in chest medicine · 2022Review
- Platelet CFTR inhibition enhances arterial thrombosis via increasing intracellular ClActa pharmacologica Sinica · 2022Article
- Utility of CD138/syndecan-1 immunohistochemistry for localization of plasmacytes is tissue-dependent in B6 mice.BMC research notes · 2022Article
- Role of LL-37 in thrombotic complications in patients with COVID-19.Cellular and molecular life sciences : CMLS · 2022Article
- Therapeutic CFTR Correction Normalizes Systemic and Lung-Specific S1P Level Alterations Associated with Heart Failure.International journal of molecular sciences · 2022Article
- Trpc6 gain-of-function disease mutation enhances phosphatidylserine exposure in murine platelets.PloS one · 2022Article
- TRPC6, a therapeutic target for pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Review
- S100A8 may govern hyper-inflammation in severe COVID-19.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Cystic fibrosis (CF) lung disease is characterized by an inflammatory response that can lead to terminal respiratory failure. The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunctional CFTR in platelets, which are key participants in immune responses, is a central determinant of CF inflammation. We found that deletion of CFTR in platelets produced exaggerated acute lung inflammation and platelet activation after intratracheal LPS or Pseudomonas aeruginosa challenge. CFTR loss of function in mouse or human platelets resulted in agonist-induced hyperactivation and increased calcium entry into platelets. Inhibition of the transient receptor potential cation channel 6 (TRPC6) reduced platelet activation and calcium flux, and reduced lung injury in CF mice after intratracheal LPS or Pseudomonas aeruginosa challenge. CF subjects receiving CFTR modulator therapy showed partial restoration of CFTR function in platelets, which may be a convenient approach to monitoring biological responses to CFTR modulators. We conclude that CFTR dysfunction in platelets produces aberrant TRPC6-dependent platelet activation, which is a major driver of CF lung inflammation and impaired bacterial clearance. Platelets and TRPC6 are what we believe to be novel therapeutic targets in the treatment of CF lung disease.
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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.