Diverse progenitor cells preserve salivary gland ductal architecture after radiation induced damage DOI Creative Commons
Alison J. May, Noel Cruz‐Pacheco, Elaine Emmerson

et al.

Development, Journal Year: 2018, Volume and Issue: unknown

Published: Jan. 1, 2018

The ductal system of the salivary gland has long been postulated to be resistant radiation-induced damage, a common side effect incurred by head and neck cancer patients receiving radiotherapy. Yet, whether ducts are capable regenerating after genotoxic injury, or damage cells induces lineage plasticity, as reported in other organ systems, remains unknown. Here, using murine gland, we show that two progenitor populations, marked exclusively KRT14 KIT, maintain non-overlapping compartments radiation exposure but do so through distinct cellular mechanisms.

Language: Английский

The physiology of salivary secretion DOI Open Access
Gordon Proctor

Periodontology 2000, Journal Year: 2015, Volume and Issue: 70(1), P. 11 - 25

Published: Dec. 10, 2015

Abstract Saliva in the mouth is a biofluid produced mainly by three pairs of major salivary glands – submandibular, parotid and sublingual along with secretions from many minor submucosal glands. Salivary gland secretion nerve‐mediated reflex volume saliva secreted dependent on intensity type taste chemosensory, masticatory or tactile stimulation. Long periods low (resting unstimulated) flow are broken short high flow, which stimulated mastication. The modulated nerve signals other centers central nervous system, most obvious as hyposalivation at times anxiety. An example neurohormonal influences circadian rhythm, affects ionic composition. Cholinergic parasympathetic adrenergic sympathetic autonomic nerves evoke secretion, signaling through muscarinic M3 adrenoceptors acinar cells leading to fluid proteins. chloride sodium secreting, isotonic rendered hypotonic duct it flows mouth. proteins present glands, creating viscoelasticity enabling coating oral surfaces saliva. films essential for maintaining health regulating microbiome. contains range validated potential disease biomarkers derived epithelial cells, neutrophils, microbiome, gingival crevicular serum. For example, cortisol levels used assessment stress, matrix metalloproteinases‐8 ‐9 appear be promising markers caries periodontal disease, panel mRNA has been proposed marker squamous cell carcinoma. Understanding mechanisms components enter an important aspect validating their use disease.

Language: Английский

Citations

440

The SLC26 gene family of anion transporters and channels DOI
Seth L. Alper, Alok K. Sharma

Molecular Aspects of Medicine, Journal Year: 2013, Volume and Issue: 34(2-3), P. 494 - 515

Published: March 16, 2013

Language: Английский

Citations

357

Role of CFTR in epithelial physiology DOI Creative Commons
Vinciane Saint‐Criq, Michael A. Gray

Cellular and Molecular Life Sciences, Journal Year: 2016, Volume and Issue: 74(1), P. 93 - 115

Published: Oct. 6, 2016

Salt and fluid absorption secretion are two processes that fundamental to epithelial function whole body homeostasis, as such tightly regulated in tissues. The CFTR anion channel plays a major role regulating both diverse range of tissues, including the airways, GI reproductive tracts, sweat salivary glands. It is not surprising then defects linked disease, life-threatening secretory diarrhoeas, cholera, well inherited cystic fibrosis (CF), one most common life-limiting genetic diseases Caucasian populations. More recently, dysfunction has also been implicated pathogenesis acute pancreatitis, chronic obstructive pulmonary disease (COPD), hyper-responsiveness asthma, underscoring its health disease. regulates many mechanisms physiology, maintaining surface hydration luminal pH. Indeed, recent studies have identified pH an important arbiter barrier innate defence, particularly airways tract. In this chapter, we will illustrate different operational roles by describing characteristics three tissues: pancreas, gland.

Language: Английский

Citations

357

Genetic Risk Factors for Pancreatic Disorders DOI Open Access
David C. Whitcomb

Gastroenterology, Journal Year: 2013, Volume and Issue: 144(6), P. 1292 - 1302

Published: April 24, 2013

Language: Английский

Citations

280

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters DOI
Mark D. Parker, Walter F. Boron

Physiological Reviews, Journal Year: 2013, Volume and Issue: 93(2), P. 803 - 959

Published: April 1, 2013

The mammalian Slc4 (Solute carrier 4) family of transporters is a functionally diverse group 10 multi-spanning membrane proteins that includes three Cl-HCO3 exchangers (AE1-3), five Na(+)-coupled HCO3(-) (NCBTs), and two other unusual members (AE4, BTR1). In this review, we mainly focus on the NCBTs-NBCe1, NBCe2, NBCn1, NDCBE, NBCn2. Each plays specialized role in maintaining intracellular pH and, by contributing to movement across epithelia, whole-body otherwise epithelial transport. Disruptions involving NCBT genes are linked blindness, deafness, proximal renal tubular acidosis, mental retardation, epilepsy. We also review AE1-3, AE4, BTR1, addressing their relevance study NCBTs. This draws together recent advances our understanding phylogenetic origins physiological NCBTs progenitors. Underlying these progress such disciplines as physiology, molecular biology, genetics, immunocytochemistry, proteomics, structural biology. highlights key similarities differences between individual encode them clarifies sometimes confusing nomenclature.

Language: Английский

Citations

265

Salivary Secretion: Mechanism and Neural Regulation DOI
Gordon Proctor, Guy H. Carpenter

Monographs in oral science, Journal Year: 2014, Volume and Issue: unknown, P. 14 - 29

Published: Jan. 1, 2014

Maintenance of a film saliva on oral surfaces is dependent upon nerve-mediated, reflex salivary gland secretion. Afferent signalling arises from taste, olfaction and mastication modified by other centres in the central nervous system before efferent signals are delivered to glands autonomic nerves. Salivary fluid secretion largely cholinergic parasympathetic nerves whilst protein content additionally neuropeptides and, major (parotid, submandibular sublingual) glands, sympathetic release noradrenaline. There have been significant recent advances our understanding membrane transport proteins involved intracellular calcium acinar cells response nerve stimulation ion responsible for cell saliva. retain an ability regenerate following extreme atrophy, important role both development maintenance long-term normal function. Continued nerve-mediated regulation should help strategies preventing chronic dryness resulting drugs or atrophic disease associated with inflammation irradiation.

Language: Английский

Citations

243

Structure, Gating, and Regulation of the CFTR Anion Channel DOI Open Access
László Csanády, Paola Vergani,

David C. Gadsby

et al.

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 707 - 738

Published: Dec. 5, 2018

The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the ATP binding cassette (ABC) transporter superfamily but functions as an anion channel crucial for salt and water transport across epithelial cells. CFTR dysfunction, because of mutations, causes (CF). anion-selective pore protein is formed by its two domains (TMDs) regulated cytosolic domains: nucleotide (NBDs) a regulatory (R) domain. Channel activation requires phosphorylation R domain cAMP–dependent kinase (PKA), opening closing (gating) phosphorylated channels driven hydrolysis at NBDs. This review summarizes available information on structure mechanism protein, with particular focus atomic-level insight gained from recent cryo-electron microscopic structures molecular mechanisms gating regulation. pharmacological small molecules targeting CFTR’s ion function, aimed treating patients suffering CF other diseases, are briefly discussed.

Language: Английский

Citations

213

Airway Gland Structure and Function DOI Open Access

J. H. Widdicombe,

Jeffrey J. Wine

Physiological Reviews, Journal Year: 2015, Volume and Issue: 95(4), P. 1241 - 1319

Published: Sept. 3, 2015

Submucosal glands contribute to airway surface liquid (ASL), a film that protects all surfaces. Glandular mucus comprises electrolytes, water, the gel-forming mucin MUC5B, and hundreds of different proteins with diverse protective functions. Gland volume per unit area mucosal correlates positively impaction rate inhaled particles. In human main bronchi, is ∼ 50 times goblet cells, but diminish in size frequency distally. ASL its trapped particles are removed from airways by mucociliary transport. Airway have tubuloacinar structure, single terminal duct, nonciliated collecting then branching secretory tubules lined mucous cells ending serous acini. They allow for massive increase numbers mucus-producing without replacing ciliated cells. Active secretion Cl(-) HCO3 (-) produces most fluid gland secretions. Glands densely innervated tonically active, mutually excitatory intrinsic neurons. Most secreted constitutively vivo, large, transient increases produced emergency reflex drive vagus. Elevations [cAMP]i [Ca(2+)]i coordinate electrolyte macromolecular probably occur together baseline activity cholinergic elevation being mainly responsive secretion. Altered submucosal function contributes pathology obstructive diseases, an early stage pathogenesis only cystic fibrosis.

Language: Английский

Citations

184

Physiology, Pathology and Regeneration of Salivary Glands DOI Creative Commons
Cristina Porcheri, Thimios A. Mitsiadis

Cells, Journal Year: 2019, Volume and Issue: 8(9), P. 976 - 976

Published: Aug. 26, 2019

Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune infections and physical traumas, can alter functionality these glands, greatly impacting quality life patients. To date, no definitive therapeutic approach compensate impairment salivary treatment purely symptomatic. Understanding cellular molecular control function is, therefore, highly relevant for purposes. In this review, we provide a starting platform future studies basic biology clinical research, reporting classical ideas on gland physiology recently developed technology to guide regeneration, reconstruction substitution functional organs.

Language: Английский

Citations

153

The SLC9A-C Mammalian Na+/H+Exchanger Family: Molecules, Mechanisms, and Physiology DOI
Stine F. Pedersen, Laurent Counillon

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(4), P. 2015 - 2113

Published: Sept. 11, 2019

Na+/H+ exchangers play pivotal roles in the control of cell and tissue pH by mediating electroneutral exchange Na+ H+ across cellular membranes. They belong to an ancient family highly evolutionarily conserved proteins, they essential physiological all phyla. In this review, we focus on mammalian (NHEs), solute carrier (SLC) 9 family. This transporters constitutes three branches: SLC9A, -B, -C. Within these, each isoform exhibits distinct expression profiles, regulation, roles. Some these are studied, with hundreds original articles, some still only rudimentarily understood. present discuss pioneering work as well current state-of-the-art research NHEs. We aim provide reader a comprehensive view core knowledge recent insights into member, from gene organization over protein structure regulation pathophysiological Particular attention is given integrated physiology NHEs main organ systems. several novel analyses useful overviews, pinpoint remaining enigmas, which hope will inspire versatile proteins.

Language: Английский

Citations

148