Acinar cell
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Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress Open
Significance This work identifies autophagy as an essential homeostatic process that maintains pancreatic acinar cell function. By preventing endoplasmic reticulum stress, reactive oxygen species accumulation, and DNA damage, basal autopha…
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Piezo1 is a mechanically activated ion channel and mediates pressure induced pancreatitis Open
Merely touching the pancreas can lead to premature zymogen activation and pancreatitis but the mechanism is not completely understood. Here we demonstrate that pancreatic acinar cells express the mechanoreceptor Piezo1 and application of p…
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Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP Open
This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease.
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Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells’ heterogeneity Open
Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from preinvasive stages to tumor formation. Using a reporter…
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TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation Open
Elevated pressure in the pancreatic gland is the central cause of pancreatitis following abdominal trauma, surgery, endoscopic retrograde cholangiopancreatography, and gallstones. In the pancreas, excessive intracellular calcium causes mit…
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The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma Open
Understanding the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) may provide therapeutic strategies for this deadly disease. Recently, we and others made the surprising finding that PDAC and its preinvasive precursor…
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Lysosome-Associated Membrane Proteins (LAMP) Maintain Pancreatic Acinar Cell Homeostasis: LAMP-2–Deficient Mice Develop Pancreatitis Open
The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis, and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice wi…
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Cell of origin affects tumour development and phenotype in pancreatic ductal adenocarcinoma Open
Objective Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumour thought to arise from ductal cells via pancreatic intraepithelial neoplasia (PanIN) precursor lesions. Modelling of different genetic events in mice suggests b…
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Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis Open
Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreat…
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Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis Open
Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient…
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Acinar cell NLRP3 inflammasome and gasdermin D (GSDMD) activation mediates pyroptosis and systemic inflammation in acute pancreatitis Open
Background and Purpose Pyroptosis is a lytic form of pro‐inflammatory cell death characterised as caspase 1 dependent with canonical NLRP3 inflammasome‐induced gasdermin D (GSDMD) activation. We aimed to investigate the role of acinar pyro…
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The Orai Ca<sup>2+</sup> channel inhibitor CM4620 targets both parenchymal and immune cells to reduce inflammation in experimental acute pancreatitis Open
Key points This work confirms previous reports that CM4620, a small molecule inhibitor of Ca 2+ entry via store operated Ca 2+ entry (SOCE) channels formed by stromal interaction molecule 1 (STIM1)/Orai complexes, attenuates acinar cell pa…
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Transgenic expression of GFP-LC3 perturbs autophagy in exocrine pancreas and acute pancreatitis responses in mice Open
Pancreatitis is a common, sometimes fatal, disease of exocrine pancreas, initiated by damaged acinar cells. Recent studies implicate disordered macroautophagy/autophagy in pancreatitis pathogenesis. ATG8/LC3 protein is critical for autopha…
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Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia Open
The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutat…
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SOX2 regulates acinar cell development in the salivary gland Open
Acinar cells play an essential role in the secretory function of exocrine organs. Despite this requirement, how acinar cells are generated during organogenesis is unclear. Using the acini-ductal network of the developing human and murine s…
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Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2‐Mediated Oxidative Stress and NLRP3 Inflammatory Pathway Open
Acute pancreatitis (AP) is characterized by early activation of intra‐acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is…
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Transcriptional Maintenance of Pancreatic Acinar Identity, Differentiation, and Homeostasis by PTF1A Open
Maintenance of cell type identity is crucial for health, yet little is known of the regulation that sustains the long-term stability of differentiated phenotypes. To investigate the roles that key transcriptional regulators play in adult d…
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ARID1A, a SWI/SNF subunit, is critical to acinar cell homeostasis and regeneration and is a barrier to transformation and epithelial-mesenchymal transition in the pancreas Open
Objective Here, we evaluate the contribution of AT-rich interaction domain-containing protein 1A ( ARID1A ), the most frequently mutated member of the SWItch/sucrose non-fermentable (SWI/SNF) complex, in pancreatic homeostasis and pancreat…
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Interleukin 22 Signaling Regulates Acinar Cell Plasticity to Promote Pancreatic Tumor Development in Mice Open
We found levels of IL22 to be increased during pancreatitis and pancreatic tumor development and to be required for tumor development and progression in mice. IL22 promotes acinar to ductal metaplasia, stem cell features, and increased exp…
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Intracellular Ca2+ Signalling in the Pathogenesis of Acute Pancreatitis: Recent Advances and Translational Perspectives Open
Intracellular Ca2+ signalling is a major signal transductional pathway in non-excitable cells, responsible for the regulation of a variety of physiological functions. In the secretory epithelial cells of the exocrine pancreas, such as acin…
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In vivo reprogramming drives Kras-induced cancer development Open
The faithful shutdown of the somatic program occurs in the early stage of reprogramming. Here, we examined the effect of in vivo reprogramming on Kras -induced cancer development. We show that the transient expression of reprogramming fact…
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Functional Differences in the Acinar Cells of the Murine Major Salivary Glands Open
In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl …
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Mogroside IIE Inhibits Digestive Enzymes via Suppression of Interleukin 9/Interleukin 9 Receptor Signalling in Acute Pancreatitis Open
The incidence of pancreatitis (AP) is increasing and there is no specific treatment available. Intracellular digestive enzyme activation is a key event in the pathogenesis of AP downstream of cytosolic calcium overload and impaired autopha…
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Pancreatic panniculitis in a patient with pancreatic-type acinar cell carcinoma of the liver – case report and review of literature Open
Pancreatic panniculitis should always be included in the differential diagnosis of lipolytic panniculitic lesions. It can be regarded as a facultative paraneoplastic phenomenon. When suspected, a thorough work-up for identification of the …
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“Heat shock protein 70 in pancreatic diseases: Friend or foe” Open
The heat shock response in pancreatitis that is activated via HSP70 protects acinar cells through multiple simultaneous mechanisms. It inhibits trypsinogen activation and modulates NF‐κB signaling to limit acinar cell injury. On the other …
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Recent Insights Into the Pathogenic Mechanism of Pancreatitis Open
Acute pancreatitis (AP) is a potentially lethal inflammatory disease that lacks specific therapy. Damaged pancreatic acinar cells are believed to be the site of AP initiation. The primary function of these cells is the synthesis, storage, …
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Tuft Cell Formation Reflects Epithelial Plasticity in Pancreatic Injury: Implications for Modeling Human Pancreatitis Open
Chronic pancreatitis, a known risk factor for the development of pancreatic ductal adenocarcinoma (PDA), is a serious, widespread medical condition characterized by inflammation, fibrosis, and acinar to ductal metaplasia (ADM). ADM is a ce…
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TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells Open
Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM…
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Acanthopanax<i>versus</i>3-Methyladenine Ameliorates Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting the Autophagic Pathway in Rats Open
Objectives . To observe the therapeutic effects of Acanthopanax and 3-methyladenine against severe acute pancreatitis (SAP). Methods . Sodium taurocholate-induced SAP rats were equally randomized into a SAP group, an Acanthopanax group, an…
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Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model Open
Acute pancreatitis (AP) is a common digestive disease characterized by inflammation of the pancreas. MiR-155 plays a role in promoting inflammation and inhibiting the activation of anti-inflammatory pathways. Impaired autophagy could promo…