scholarly journals Diverse progenitor cells preserve salivary gland ductal architecture after radiation induced damage

2018 ◽  
Author(s):  
Alison J. May ◽  
Noel Cruz-Pacheco ◽  
Elaine Emmerson ◽  
Kerstin Seidel ◽  
Sara Nathan ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Progenitor Cells ◽  
Tissue Architecture ◽  
Cellular Mechanisms ◽  
Ductal Cells ◽  
Differentiated Cells ◽  
Organ Systems ◽  
Radiation Induced ◽  
Summary Statement ◽  
Do So

AbstractThe ductal system of the salivary gland has long been postulated to be resistant to radiation-induced damage, a common outcome incurred by head and neck cancer patients receiving radiotherapy. Yet, whether the ducts are capable of regenerating after genotoxic injury, or if damage to ductal cells induces lineage plasticity, as has been reported in other organ systems, remains unknown. Here, we show that two ductal progenitor populations marked by KRT14 and KIT exclusively maintain non-overlapping ductal compartments after radiation exposure but do so through distinct cellular mechanisms. KRT14+ progenitor cells are fast cycling cells that proliferate in response to radiation-induced damage in a sustained manner and divide asymmetrically to produce differentiated cells of the larger granulated ducts. Conversely, KIT+ cells are long lived progenitors for the intercalated ducts that undergo few cell divisions either during homeostasis or after gamma radiation, thus maintaining ductal architecture in the near absence of cell turnover. Together, these data illustrate the regenerative capacity of the salivary ducts and highlight the heterogeneity in the damage responses used by salivary progenitor cells to maintain tissue architecture.Summary StatementThe salivary gland ductal network is maintained during homeostasis and after genotoxic injury by diverse progenitors that respond differentially to radiation induced damage.

scholarly journals Diverse progenitor cells preserve salivary gland ductal architecture after radiation-induced damage

Development ◽  
2018 ◽  
Vol 145 (21) ◽  
pp. dev166363 ◽  
Author(s):  
Alison J. May ◽  
Noel Cruz-Pacheco ◽  
Elaine Emmerson ◽  
Eliza A. Gaylord ◽  
Kerstin Seidel ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Progenitor Cells ◽  
Radiation Induced

scholarly journals The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 855
Author(s):  
Paola Serrano Martinez ◽  
Lorena Giuranno ◽  
Marc Vooijs ◽  
Robert P. Coppes
Keyword(s):  
Signaling Pathways ◽  
Progenitor Cells ◽  
Tissue Regeneration ◽  
Normal Tissue ◽  
Cellular Response ◽  
Adult Tissue ◽  
Tissue Specific ◽  
Radiation Induced

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

scholarly journals Neurofibromin expression by normal salivary glands

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Eloá Borges Luna ◽  
Pâmella Pinho Montovani ◽  
Rafaela Elvira Rozza-de-Menezes ◽  
Karin Soares Cunha
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Acinar Cells ◽  
Staining Intensity ◽  
Neurofibromatosis 1 ◽  
Tissue Type ◽  
Sublingual Gland ◽  
Minor Salivary Glands ◽  
Expression Levels ◽  
Ductal Cells

AbstractIntroductionNeurofibromin, a protein encoded by theNF1gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated.AimTo investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1.Material and methodTen samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method.ResultsNeurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34).ConclusionNeurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.

scholarly journals Radiation induced CNS toxicity – molecular and cellular mechanisms

2001 ◽  
Vol 85 (9) ◽  
pp. 1233-1239 ◽  
Author(s):  
C Belka ◽  
W Budach ◽  
R D Kortmann ◽  
M Bamberg
Keyword(s):  
Cellular Mechanisms ◽  
Radiation Induced ◽  
Cns Toxicity

Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications

2013 ◽  
Vol 93 (4) ◽  
pp. 1743-1802 ◽  
Author(s):  
Jean-Sébastien Silvestre ◽  
David M. Smadja ◽  
Bernard I. Lévy
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Vascular Wall ◽  
Arterial Disease ◽  
Cellular Mechanisms ◽  
Collateral Growth ◽  
Vessel Growth ◽  
Ischemic Diseases

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

scholarly journals The evolving definition of salivary gland stem cells

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Cecilia Rocchi ◽  
Lara Barazzuol ◽  
Rob P. Coppes
Keyword(s):  
Stem Cells ◽  
Salivary Gland ◽  
Adult Stem Cell ◽  
Cell Types ◽  
Research Field ◽  
New Therapeutic Approaches ◽  
Recent Developments ◽  
Radiation Induced ◽  
Definition Of

AbstractDysfunction of the salivary gland and irreversible hyposalivation are the main side effects of radiotherapy treatment for head and neck cancer leading to a drastic decrease of the quality of life of the patients. Approaches aimed at regenerating damaged salivary glands have been proposed as means to provide long-term restoration of tissue function in the affected patients. In studies to elucidate salivary gland regenerative mechanisms, more and more evidence suggests that salivary gland stem/progenitor cell behavior, like many other adult tissues, does not follow that of the hard-wired professional stem cells of the hematopoietic system. In this review, we provide evidence showing that several cell types within the salivary gland epithelium can serve as stem/progenitor-like cells. While these cell populations seem to function mostly as lineage-restricted progenitors during homeostasis, we indicate that upon damage specific plasticity mechanisms might be activated to take part in regeneration of the tissue. In light of these insights, we provide an overview of how recent developments in the adult stem cell research field are changing our thinking of the definition of salivary gland stem cells and their potential plasticity upon damage. These new perspectives may have important implications on the development of new therapeutic approaches to rescue radiation-induced hyposalivation.

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

Metaphase-Based Cytogenetic Approach Identifies Radiation-Induced Chromosome and Chromatid Aberrations in Zebrafish Embryos

2021 ◽  
Author(s):  
Halida Thanveer Asana Marican ◽  
Hongyuan Shen
Keyword(s):  
Animal Model ◽  
Radiation Exposure ◽  
Progenitor Cells ◽  
Chromosome Aberrations ◽  
Structural Changes ◽  
Current Knowledge ◽  
Living Organism ◽  
Zebrafish Embryos ◽  
Radiation Induced

Metaphase-based cytogenetic methods based on scoring of chromosome aberrations for the estimation of the radiation dose received provide a powerful approach for evaluating the associated risk upon radiation exposure and form the bulk of our current knowledge of radiation-induced chromosome damages. They mainly rely on inducing quiescent peripheral lymphocytes into proliferation and blocking them at metaphases to quantify the damages at the chromosome level. However, human organs and tissues demonstrate various sensitivity towards radiation and within them, self-proliferating progenitor/stem cells are believed to be the most sensitive populations. The radiation-induced chromosome aberrations in these cells remain largely unknown, especially in the context of an intact living organism. Zebrafish is an ideal animal model for research into this aspect due to their small size and the large quantities of progenitor cells present during the embryonic stages. In this study, we employ a novel metaphase-based cytogenetic approach on zebrafish embryos and demonstrate that chromosome-type and chromatid-type aberrations could be identified in progenitor cells at different cell-cycle stages at the point of radiation exposure. Our work positions zebrafish at the forefront as a useful animal model for studying radiation-induced chromosome structural changes in vivo.

Cannabinoids and myocardial ischemia: Novel insights, updated mechanisms, and implications for myocardial infarction

2021 ◽  
Vol 28 ◽  
Author(s):  
Karim Seif El-Dahan ◽  
Dima Machtoub ◽  
Gaelle Massoud ◽  
Suzanne A. Nasser ◽  
Bassam Hamam ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Illicit Drugs ◽  
Supply And Demand ◽  
Health Benefits ◽  
Cell Types ◽  
Cellular Mechanisms ◽  
Potential Health ◽  
Organ Systems ◽  
Increased Risk

: Cannabis is the most widely trafficked and abused illicit drug due to its calming psychoactive properties. It has been increasingly recognized as having potential health benefits and relatively less adverse health effects as compared to other illicit drugs; however, growing evidence clearly indicates that cannabis is associated with considerable adverse cardiovascular events. Recent studies have linked cannabis use to myocardial infarction (MI); yet, very little is known about the underlying mechanisms. A MI is a cardiovascular disease characterized by a mismatch in the oxygen supply and demand of the heart, resulting in ischemia and subsequent necrosis of the myocardium. Since cannabis is increasingly being considered a risk factor for MI, there is a growing need for better appreciating its potential health benefits and consequences. Here, we discuss the cellular mechanisms of cannabis that lead to an increased risk of MI. We provide a thorough and critical analysis of cannabinoids’ actions, which include modulation of adipocyte biology, regional fat distribution, and atherosclerosis, as well as precipitation of hemodynamic stressors relevant in the setting of a MI. By critically dissecting the modulation of signaling pathways in multiple cell types, this paper highlights the mechanisms through which cannabis may trigger life-threatening cardiovascular events. This then provides a framework for future pharmacological studies which can identify targets or develop drugs that modulate cannabis’ effects on the cardiovascular system as well as other organ systems. Cannabis’ impact on the autonomic outflow, vascular smooth muscle cells, myocardium, cortisol levels and other hemodynamic changes are also mechanistically reviewed.

scholarly journals Cross-talk inhibition between 5-HT2B and 5-HT7 receptors in phrenic motor facilitation via NADPH oxidase and PKA

2018 ◽  
Vol 314 (5) ◽  
pp. R709-R715 ◽  
Author(s):  
Raphael R. Perim ◽  
Daryl P. Fields ◽  
Gordon S. Mitchell
Keyword(s):  
Nadph Oxidase ◽  
Cross Talk ◽  
Serotonin Receptor ◽  
Receptor Activation ◽  
Cellular Mechanisms ◽  
Subtype B ◽  
Receptor Inhibition ◽  
Subtype A ◽  
Do So

Intermittent spinal serotonin receptor activation elicits phrenic motor facilitation (pMF), a form of spinal respiratory motor plasticity. Episodic activation of either serotonin type 2 (5-HT2) or type 7 (5-HT7) receptors elicits pMF, although they do so via distinct cellular mechanisms known as the Q (5-HT2) and S (5-HT7) pathways to pMF. When coactivated, these pathways interact via mutual cross-talk inhibition. Although we have a rudimentary understanding of mechanisms mediating cross-talk interactions between spinal 5-HT2 subtype A (5-HT2A) and 5-HT7 receptor activation, we do not know if similar interactions exist between 5-HT2 subtype B (5-HT2B) and 5-HT7 receptors. We confirmed that either spinal 5-HT2B or 5-HT7 receptor activation alone elicits pMF and tested the hypotheses that 1) concurrent activation of both receptors suppresses pMF due to cross-talk inhibition; 2) 5-HT7 receptor inhibition of 5-HT2B receptor-induced pMF requires protein kinase A (PKA) activity; and 3) 5-HT2B receptor inhibition of 5-HT7 receptor-induced pMF requires NADPH oxidase (NOX) activity. Selective 5-HT2B and 5-HT7 receptor agonists were administered intrathecally at C4 (3 injections, 5-min intervals) to anesthetized, paralyzed, and ventilated rats. Whereas integrated phrenic nerve burst amplitude increased after selective spinal 5-HT2B or 5-HT7 receptor activation alone (i.e., pMF), pMF was no longer observed with concurrent 5-HT2B and 5-HT7 receptor agonist administration. With concurrent receptor activation, pMF was rescued by inhibiting either NOX or PKA activity, demonstrating their roles in cross-talk inhibition between these pathways to pMF. This report demonstrates cross-talk inhibition between 5-HT2B- and 5-HT7 receptor-induced pMF and that NOX and PKA activity are necessary for that cross-talk inhibition.

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