Parenchymal pressure injury Ca2+ entry mechanism in pancreatitis

doi:10.1016/j.ceca.2020.102208

Cell Calcium

Volume 88, June 2020, 102208

https://doi.org/10.1016/j.ceca.2020.102208 Get rights and content

Abstract

Pancreatic trauma and high parenchymal pressure have been found to open Piezo1 plasma membrane Ca²⁺ channels to such an extent that transient receptor potential vanilloid type 4 channels also open to further Ca²⁺ entry, overloading the cell with Ca²⁺ to induce acute pancreatitis (Swain et al, J Clin Invest, 2020). Elucidation of this mechanism is an important step in understanding pancreatitis and opens up new possibilities for prevention and treatment.

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Declaration of Competing Interest

RS has received research support and/or funding from Calcimedica, Cypralis, GlaxoSmithKline, MSD/Merck and Novartis, has been a consultant for AbbVie, Calcimedica, Cypralis, Eagle Pharmaceuticals, Novartis and Takeda (all funds to the University of Liverpool), and is collaborating in the IMI2 TransBioLine project with multiple public and private institutions including Janssen, Lilly, MSD/Merck, Novartis, Pfizer, Roche and Sanofi-Aventis.

Acknowledgements

RS is funded by the U.K. Medical Research Council and National Institute for Health Research, European Union Innovative Medicines Initiative, GlaxoSmithKline PLC and Hampson Trust, and is an NIHR Senior Investigator.

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Cited by (4)

Establishment of a multifunctional impact system and a study of a pancreatic trauma model in rats based on controlling the injury area
2023, Heliyon
At present, basic scientific research on pancreatic trauma is rare due to the lack of ideal animal models and modeling equipment for pancreatic trauma. Therefore, we intend to develop a multifunctional impact system with simple operation, diverse impact and accurate measurement and to establish a rat pancreatic trauma model based on injury area control by using the system.
The impactor was designed based on the convenience of the impact energy acquisition, the diversity of the impact operation, and the precision of the impact strength parameter measurement by the team. The efficacy and stability/repeatability of the impactor were preliminarily evaluated. An impact head with different impact areas (3 cm² and 6 cm²) of the impactor was used to squeeze the rat pancreas in the abdomen to form different injury areas under a pressure of 400 kPa. The efficacy features of this trauma model were evaluated by detecting the outcomes of pathology and biochemistry at 24 h after injury in the two groups. Furthermore, these changes were also evaluated at 6 h, 24 h, 48 h and 72 h after injury in the 3 cm² trauma group.
Multifunctional impactors were successfully explored. The impact force was continuously adjustable with a range of 0–200 kg. The compression and extrusion stress ranges were continuously adjustable from 0 to 100 kg. System adjustment verified that the impactor had fine efficacy (P < 0.05) and stability/repeatability (P > 0.05). Compared with the control group, rats in the pancreatic trauma group with different injury areas exhibited obvious injuries (P < 0.05), and compared with the 3 cm² trauma group, the 6 cm² trauma group exhibited the more severe injury (P < 0.05). After modeling, the injury characteristics at different time points showed stable differences(P < 0.05).
A rat pancreatic trauma model based on injury area control was successfully established using the impactor developed in this study. This model is simple, effective, controllable, and suitable for animal experimental research on pancreatic trauma.
Acute pancreatitis: Pathogenesis and emerging therapies
2024, Journal of Pancreatology
Acute Pancreatitis: Diagnosis and Treatment
2022, Drugs
Critical thresholds: Key to unlocking the door to the prevention and specific treatments for acute pancreatitis
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CommentaryParenchymal pressure injury Ca2+ entry mechanism in pancreatitis

Abstract

Section snippets

Declaration of Competing Interest

Acknowledgements

Gastroenterology

Cell Metab

Management of severe acute pancreatitis

BMJ

TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation

J Clin Invest

Inhibitors of ORAI1 prevent cytosolic calcium-associated injury of human pancreatic acinar cells and acute pancreatitis in 3 mouse models

Gastroenterology

Commentary
Parenchymal pressure injury Ca²⁺ entry mechanism in pancreatitis