ArticleFrontiers in physiology2012
Protein kinase d regulates cell death pathways in experimental pancreatitis.
Article in Frontiers in physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Protein kinase D1 - A targetable mediator of pancreatic cancer development.Biochimica et biophysica acta. Molecular cell research · 2024Review
- β-Carotene Supplementation Improves Pancreas Function during Moderate Ethanol Consumption: Initial Characterization from a Morphological Overview.International journal of molecular sciences · 2024Article
- Loss of Protein Kinase D2 Activity Protects Against Bleomycin-Induced Dermal Fibrosis in Mice.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Small Molecule Inhibitors of Protein Kinase D: Early Development, Current Approaches, and Future Directions.Journal of medicinal chemistry · 2023Review
- Protein kinase D: A therapeutic target in experimental alcoholic pancreatitis.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway.Cell death & disease · 2022Article
- Small Extracellular Vesicles Propagate the Inflammatory Response After Trauma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- N-glycosylation of somatostatin receptor type 2 protects rats from acute pancreatitis.Annals of translational medicine · 2021Article
- Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ.International journal of molecular sciences · 2021Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Pancreas-specific deletion of protein kinase D attenuates inflammation, necrosis, and severity of acute pancreatitis.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice.Hepatology (Baltimore, Md.) · 2020Article
- What Do We Currently Know about the Pathophysiology of Alcoholic Pancreatitis: A Brief Review.Visceral medicine · 2020Review
- Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway.Apoptosis : an international journal on programmed cell death · 2020Article
- Review
- Acute Pancreatitis: A Multifaceted Set of Organelle and Cellular Interactions.Gastroenterology · 2019Review
- Angiogenic function of astragaloside IV in rats with myocardial infarction occurs via the PKD1-HDAC5-VEGF pathway.Experimental and therapeutic medicine · 2019Article
- Protein kinase D signaling in cancer: A friend or foe?Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity.Cell death & disease · 2017Article
- Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-kappaB Activation and Attenuate the Severity of Rat Cerulein Pancreatitis.Frontiers in physiology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Inflammation and acinar cell necrosis are two major pathological responses of acute pancreatitis, a serious disorder with no current therapies directed to its molecular pathogenesis. Serine/threonine protein kinase D family, which includes PKD/PKD1, PKD2, and PKD3, has been increasingly implicated in the regulation of multiple physiological and pathophysiological effects. We recently reported that PKD/PKD1, the predominant PKD isoform expressed in rat pancreatic acinar cells, mediates early events of pancreatitis including NF-κB activation and inappropriate intracellular digestive enzyme activation. In current studies, we investigated the role and mechanisms of PKD/PKD1 in the regulation of necrosis in pancreatic acinar cells by using two novel small molecule PKD inhibitors CID755673 and CRT0066101 and molecular approaches in in vitro and in vivo experimental models of acute pancreatitis. Our results demonstrated that both CID755673 and CRT0066101 are PKD-specific inhibitors and that PKD/PKD1 inhibition by either the chemical inhibitors or specific PKD/PKD1 siRNAs attenuated necrosis while promoting apoptosis induced by pathological doses of cholecystokinin-octapeptide (CCK) in pancreatic acinar cells. Conversely, up-regulation of PKD expression in pancreatic acinar cells increased necrosis and decreased apoptosis. We further showed that PKD/PKD1 regulated several key cell death signals including inhibitors of apoptotic proteins, caspases, receptor-interacting protein kinase 1 to promote necrosis. PKD/PKD1 inhibition by CID755673 significantly ameliorated necrosis and severity of pancreatitis in an in vivo experimental model of acute pancreatitis. Thus, our studies indicate that PKD/PKD1 is a key mediator of necrosis in acute pancreatitis and that PKD/PKD1 may represent a potential therapeutic target in 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.