ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
Protease activation during in vivo pancreatitis is dependent on calcineurin activation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 75 citations in OpenAlex.
- Role of serine/threonine phosphatases 1 and 2A in pancreatic acinar fluid and electrolyte secretion.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Elucidation of roles of serine/threonine phosphatases PP1 and PP2A in mediating CCK-stimulated growth and enzyme secretion in pancreatic acinar cells.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Recurrent acute pancreatitis and primary hyperparathyroidism in patients presenting to the emergency department: Diagnostic challenges.World journal of clinical cases · 2025Article
- Signaling Pathways Involved in Acute Pancreatitis.Journal of inflammation research · 2025Review
- The mechanism of short-chain fatty acid in hypertriglyceridemic pancreatitis.Frontiers in microbiology · 2025Article
- GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis.Nature communications · 2024Article
- Long-chain fatty acids - The turning point between 'mild' and 'severe' acute pancreatitis.Heliyon · 2024Review
- Idiopathic acute pancreatitis (IAP)-a review of the literature and algorithm proposed for the diagnostic work-up of IAP.Translational gastroenterology and hepatology · 2024Review
- Alterations of oral microbiota are associated with the development and severity of acute pancreatitis.Journal of oral microbiology · 2023Article
- Qingyi decoction attenuates intestinal epithelial cell injuryWorld journal of gastroenterology · 2022Article
- Primary hyperparathyroidism presenting as acute pancreatitis: An institutional experience with review of the literature.World journal of gastrointestinal pharmacology and therapeutics · 2022Article
- Hypercalcemia - An enigmatic cause of acute pancreatitis.Journal of clinical and translational research · 2022Article
- New insights into the etiology, risk factors, and pathogenesis of pancreatitis in dogs: Potential impacts on clinical practice.Journal of veterinary internal medicine · 2022Review
- Effect of calcineurin inhibitor on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with liver transplantation: a propensity-matched cohort study.The Korean journal of internal medicine · 2020Article
- The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source.Gastroenterology · 2020Article
- Review
- Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice.Journal of gastroenterology · 2019Article
- Familial Pancreatic Ductal Adenocarcinoma.The American journal of pathology · 2019Review
- Research Progress on the Relationship Between Acute Pancreatitis and Calcium Overload in Acinar Cells.Digestive diseases and sciences · 2019Review
- The Dual Role of HMGB1 in Pancreatic Cancer.Journal of pancreatology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The premature activation of digestive proenzymes, specifically proteases, within the pancreatic acinar cell is an early and critical event during acute pancreatitis. Our previous studies demonstrate that this activation requires a distinct pathological rise in cytosolic Ca(2+). Furthermore, we have shown that a target of aberrant Ca(2+) in acinar cells is the Ca(2+)/calmodulin-dependent phosphatase calcineurin (PP2B). In this study, we hypothesized that PP2B mediates in vivo protease activation and pancreatitis severity. To test this, pancreatitis was induced in mice over 8 h by administering hourly intraperitoneal injections of the cholecystokinin analog caerulein (50 microg/kg). Treatment with the PP2B inhibitor FK506 at 1 and 8 h after pancreatitis induction reduced trypsin activities by greater than 50% (P < 0.005). Serum amylase and IL-6 was reduced by 86 and 84% relative to baseline (P < 0.0005) at 8 h, respectively. Histological severity of pancreatitis, graded on the basis of pancreatic edema, acinar cell vacuolization, inflammation, and apoptosis, was reduced early in the course of pancreatitis. Myeloperoxidase activity from both pancreas and lung was reduced by 93 and 83% relative to baseline, respectively (P < 0.05). These data suggest that PP2B is an important target of the aberrant acinar cell Ca(2+) rise associated with pathological protease activation and pancreatitis.
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