ArticleJCI insight2023
Orai1 calcium channel inhibition prevents progression of chronic pancreatitis.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed.
- TH1177, Clemastine, and Benzhydryl Derivatives Act as Novel Extracellular Blockers of ORAI Channels.Biomolecules · 2026Article
- CRAC channels as targets for immunotherapy.Current opinion in immunology · 2026Review
- Orai1 is required for CabioRxiv : the preprint server for biology · 2026Article
- Personalizing treatment of pancreatitis-associated chronic pain: the need for an integrated omics approach.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- pH-Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma.Acta physiologica (Oxford, England) · 2026Review
- Investigating the role of lncRNA SNHG14 in early diagnosis and prognosis of acute pancreatitis: a bioinformatics exploration.Hereditas · 2026Article
- Targeted therapeutics for pancreatitis.Frontiers in physiology · 2026Review
- Monocellular and Multicellular Parasites Infesting Humans: A Review of Calcium Ion Mechanisms.Biomedicines · 2025Review
- 1,2,3,4-Dithiadiazole Derivative 3-(4-Nitrophenyl)-5-Phenyl-3H-1,2,3,4-Dithiadiazole-2-Oxide Affects Both STIM1- and STIM2-Dependent Store-Operated Calcium Channels.Bulletin of experimental biology and medicine · 2025Article
- Sodium aescinate promotes apoptosis of pancreatic stellate cells and alleviates pancreatic fibrosis by inhibiting the PI3K/Akt/FOXO1 signaling pathways.Frontiers in pharmacology · 2025Article
- Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis.Scientific reports · 2024Article
- Fibroblast subtypes in pancreatic cancer and pancreatitis: from mechanisms to therapeutic strategies.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases.Journal of Crohn's & colitis · 2024Article
- Activation and Regulation of Pancreatic Stellate Cells in Chronic Pancreatic Fibrosis: A Potential Therapeutic Approach for Chronic Pancreatitis.Biomedicines · 2024Review
- Store-Operated CaContact (Thousand Oaks (Ventura County, Calif.))Review
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with recurrent acute pancreatitis (RAP) are at significant risk of developing early chronic pancreatitis (CP), which progresses into irreversible, end-stage CP with severe symptoms. There is no specific therapy in RAP or in early CP that may hinder disease progression. The pathogenesis of CP is complex and involves interactions among multiple cell types, including pancreatic acinar, ductal, and stellate cells (PSC). Therefore, it is pivotal to identify common pathogenic pathways in these cells that could be targeted pharmacologically. The Orai1-mediated store-operated Ca2+ entry (SOCE) is a ubiquitous signaling mechanism that may become overactivated in pathological states resulting in intracellular Ca2+ overload. In this study, we used ex vivo and in vivo preclinical disease models to demonstrate that Orai1 inhibition prevents progression of RAP and early CP. The selective Orai1 inhibitor CM5480 restored the expression of SOCE-associated regulatory factor in acinar cells, prevented uncontrolled Ca2+ elevation, protected acinar and ductal functions, mitigated immune cell infiltration, and diminished PSC activation, proliferation, and migration. We suggest that the overactivation of Orai1 is a crucial pathogenetic event in the progression of early CP and that inhibition of Orai1 could prevent the development of end-stage CP.
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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 Socratic graph.