ArticleCellular and molecular gastroenterology and hepatology2015
Early to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar Cells.
Article in Cellular and molecular gastroenterology and hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Pathologically relevant trypsinogen activation in pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?World journal of gastroenterology · 2024Review
- Interleukin‑22 alleviates arginine‑induced pancreatic acinar cell injury via the regulation of intracellular vesicle transport system: Evidence from proteomic analysis.Experimental and therapeutic medicine · 2023Article
- Article
- Glycometabolism regulates hepatitis C virus release.PLoS pathogens · 2021Article
- Plasma membrane integrity: implications for health and disease.BMC biology · 2021Review
- Transgenic expression of GFP-LC3 perturbs autophagy in exocrine pancreas and acute pancreatitis responses in mice.Autophagy · 2020Article
- Genetics, Cell Biology, and Pathophysiology of Pancreatitis.Gastroenterology · 2019Review
- Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders.Pancreas · 2019Review
- A CaThe Journal of cell biology · 2018Article
- Article
- Article
- Human Pancreatic Acinar Cells: Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis.The American journal of pathology · 2017Article
- Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models.Scientific reports · 2017Article
- Acute acinar pancreatitis blocks vesicle-associated membrane protein 8 (VAMP8)-dependent secretion, resulting in intracellular trypsin accumulation.The Journal of biological chemistry · 2017Article
- PIKfyve inhibition increases exosome release and induces secretory autophagy.Cellular and molecular life sciences : CMLS · 2016Article
- New insights into the pathways initiating and driving pancreatitis.Current opinion in gastroenterology · 2016Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsPancreatic acinar cells have an expanded apical endosomal system, the physiological and pathophysiological significance of which is still emerging. Phosphatidylinositol-3,5-bisphosphate (PI(3,5)P
methodsInhibition of EE to LE trafficking was achieved using pharmacological inhibitors of PIKfyve, expression of dominant negative PIKfyve K1877E, or constitutively active Rab5-GTP Q79L. Anterograde endosomal trafficking was manipulated by expression of constitutively active and dominant negative Rab11a mutants. The effects of these agents on secretion, endolysosomal exocytosis of lysosome associated membrane protein (LAMP1), and trypsinogen activation in response to high-dose CCK-8, bile acids and cigarette toxin was determined.
resultsPIKfyve inhibition increased basal and stimulated secretion. Adenoviral overexpression of PIKfyve decreased secretion leading to cellular death. Expression of Rab5-GTP Q79L or Rab11a-GTP Q70L enhanced secretion. Conversely, dominant-negative Rab11a-GDP S25N reduced secretion. High-dose CCK inhibited endolysosomal exocytosis that was reversed by PIKfyve inhibition. PIKfyve inhibition blocked intracellular trypsin accumulation and cellular damage responses to high CCK-8, tobacco toxin, and bile salts in both rodent and human acini.
conclusionsThese data demonstrate that EE-LE trafficking acutely controls acinar secretion and the intracellular activation of zymogens leading to the pathogenicity of acute pancreatitis.
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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.