The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1691 - 1744

Published: May 5, 2021

This review deals with the roles of calcium ions and ATP in control normal functions different cell types exocrine pancreas as well these molecules pathophysiology acute pancreatitis. Repetitive rises local cytosolic ion concentration apical part acinar cells not only activate exocytosis but also, via an increase intramitochondrial concentration, stimulate formation that is needed to fuel energy-requiring secretion process. However, intracellular overload, resulting a global sustained elevation has opposite effect decreasing mitochondrial production, this initiates processes lead necrosis. In last few years it become possible image signaling events simultaneously acinar, stellate, immune intact lobules pancreas. disclosed by which interact each other, particularly relation initiation development By unraveling molecular mechanisms underlying disease, several promising therapeutic intervention sites have been identified. provides hope we may soon be able effectively treat often fatal disease.

Language: Английский

---

Salivary gland function, development, and regeneration

Physiological Reviews, Journal Year: 2022, Volume and Issue: 102(3), P. 1495 - 1552

Published: March 28, 2022

Salivary glands produce and secrete saliva, which is essential for maintaining oral health overall health. Understanding both the unique structure physiological function of salivary glands, as well how they are affected by disease injury, will direct development therapy to repair regenerate them. Significant recent advances, particularly in OMICS field, increase our understanding develop at cellular, molecular, genetic levels: signaling pathways involved, dynamics progenitor cell lineages development, homeostasis, regeneration, role extracellular matrix microenvironment. These provide a template gene therapies bioengineering approaches or function.

Language: Английский

---

Electrochemical sensing of analytes in saliva: Challenges, progress, and perspectives

TrAC Trends in Analytical Chemistry, Journal Year: 2023, Volume and Issue: 160, P. 116965 - 116965

Published: Feb. 13, 2023

Language: Английский

---

Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 13, 2025

Abstract The pancreas, an organ with dual functions, regulates blood glucose levels through the endocrine system by secreting hormones such as insulin and glucagon. It also aids digestion exocrine digestive enzymes. Complex interactions signaling mechanisms between functions of pancreas play a crucial role in maintaining metabolic homeostasis overall health. Compelling evidence indicates direct indirect crosstalk parts, influencing development diseases affecting both. From developmental perspective, parts share same origin—the “tip-trunk” domain. In certain circumstances, pancreatic cells may transdifferentiate into endocrine-like cells, insulin-secreting cells. Additionally, several diseases, including cancer, pancreatitis, diabetes, exhibit potential relevance to both functions. Endocrine communicate directly cytokines or indirectly regulating immune microenvironment. This affects onset progression these diseases. review summarizes history milestones findings related their embryonic development, phenotypic transformations, roles health disease, endocrine-exocrine from perspective therapeutic targets. Elucidating regulatory provide novel insights for understanding treatment

Language: Английский

---

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

PLoS Genetics, Journal Year: 2014, Volume and Issue: 10(7), P. e1004376 - e1004376

Published: July 17, 2014

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes to change permeability and conductance characteristics from chloride-preferring bicarbonate-preferring channel through unknown mechanisms. Two severe mutations (CFTRsev) cause complete loss of function result in cystic fibrosis (CF), genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, male reproductive system. We hypothesize that those disrupt the mechanisms selective, bicarbonate defect (CFTRBD) organs utilize for secretion (e.g. sinus, vas deferens) but do not typical CF. To understand structural functional requirements channel, we (a) screened 984 well-phenotyped pancreatitis cases candidate CFTRBD among 81 previously described variants; (b) conducted electrophysiology studies on clones variants found CF; (c) computationally constructed new, model molecular dynamics simulation wild-type mutant (d) tested newly defined disease non-pancreas utilizing secretion. Nine (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, D1270N) associated with CF were (OR 1.5, p = 0.002). Clones expressed HEK 293T cells had normal chloride activation. Molecular simulations suggest physical restriction altered dynamic regulation. Comparing patients controls, increased risk rhinosinusitis 2.3, p<0.005) infertility 395, p<<0.0001). pathway-activated increases are by multiple clinically significant disorders

Language: Английский

---

Purification and Ex Vivo Expansion of Fully Functional Salivary Gland Stem Cells

Stem Cell Reports, Journal Year: 2014, Volume and Issue: 3(6), P. 957 - 964

Published: Oct. 24, 2014

Hyposalivation often leads to irreversible and untreatable xerostomia. Salivary gland (SG) stem cell therapy is an attractive putative option salvage these patients but impeded by the limited availability of adult human tissue. Here, using murine SG cells, we demonstrate single-cell self-renewal, differentiation, enrichment robust in vitro expansion. Dependent on marker expression, sphere-derived single cells could be differentiated into distinct lobular or ductal/lobular organoids, suggestive progenitor potency. Expanded were able form miniglands/organoids containing multiple lineages. Expansion multipotent through serial passaging resulted selection a population, homogenous for expression (CD24hi/CD29hi). Cells highly expressing CD24 CD29 prospectively isolated efficiently restore radiation-damaged function. Our approach will facilitate use variety scientific therapeutic purposes.

Language: Английский

---

Orai1-Mediated Antimicrobial Secretion from Pancreatic Acini Shapes the Gut Microbiome and Regulates Gut Innate Immunity

Cell Metabolism, Journal Year: 2017, Volume and Issue: 25(3), P. 635 - 646

Published: March 1, 2017

Language: Английский

---

Salivary gland development: A template for regeneration

Seminars in Cell and Developmental Biology, Journal Year: 2013, Volume and Issue: 25-26, P. 52 - 60

Published: Dec. 11, 2013

Language: Английский

---

Dynamic modulation of ANO1/TMEM16A HCO ₃ ⁻ permeability by Ca ²⁺ /calmodulin

Proceedings of the National Academy of Sciences, Journal Year: 2012, Volume and Issue: 110(1), P. 360 - 365

Published: Dec. 17, 2012

Anoctamin 1 (ANO1)/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel that may play role in HCO 3 − secretion epithelial cells. Here, we report the selectivity of ANO1 dynamically regulated by Ca 2+ /calmodulin complex. Whole-cell current measurements HEK 293T cells indicated becomes highly permeable to at high [Ca ] i . Interestingly, this result was not observed excised patches, indicating involvement cytosolic factors process. Further studies revealed direct association between and calmodulin responsible for changes permeability. Calmodulin physically interacted with -dependent manner, addition recombinant side patches reversibly increased P HCO3 /P Cl In addition, -induced increase permeability reproduced mouse submandibular gland acinar cells, which plays critical fluid secretion. These results indicate can be modulated an important cellular transport, especially transepithelial

Language: Английский

---

Pancreatic pathophysiology in cystic fibrosis

The Journal of Pathology, Journal Year: 2015, Volume and Issue: 238(2), P. 311 - 320

Published: Sept. 14, 2015

Abstract The pancreas is one of the earliest, and most commonly affected, organs in patients with cystic fibrosis ( CF ). Studying pathogenesis pancreatic disease limited patients, due to its early clinical onset, co‐morbidities lack tissue samples from phases disease. In recent years, several new animal models have been developed that advanced our understanding both exocrine endocrine Additionally, these helped us better define influence lesions on progression other organs, such as gastrointestinal tract lung. Copyright © 2015 Pathological Society Great Britain Ireland. Published by John Wiley & Sons, Ltd.

Language: Английский

---