scholarly journals β-Adrenergic signaling induces Notch-mediated salivary gland progenitor cell control

Author(s):  
X. Wang ◽  
P. Serrano Martinez ◽  
J.H. Terpstra ◽  
A. Shaalan ◽  
G.B. Proctor ◽  
...  
2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Xiaohong Peng ◽  
Yi Wu ◽  
Uilke Brouwer ◽  
Thijmen van Vliet ◽  
Boshi Wang ◽  
...  

Abstract Radiotherapy for head and neck cancer is associated with impairment of salivary gland function and consequent xerostomia, which has a devastating effect on the quality of life of the patients. The mechanism of radiation-induced salivary gland damage is not completely understood. Cellular senescence is a permanent state of cell cycle arrest accompanied by a secretory phenotype which contributes to inflammation and tissue deterioration. Genotoxic stresses, including radiation-induced DNA damage, are known to induce a senescence response. Here, we show that radiation induces cellular senescence preferentially in the salivary gland stem/progenitor cell niche of mouse models and patients. Similarly, salivary gland-derived organoids show increased expression of senescence markers and pro-inflammatory senescence-associated secretory phenotype (SASP) factors after radiation exposure. Clearance of senescent cells by selective removal of p16Ink4a-positive cells by the drug ganciclovir or the senolytic drug ABT263 lead to increased stem cell self-renewal capacity as measured by organoid formation efficiency. Additionally, pharmacological treatment with ABT263 in mice irradiated to the salivary glands mitigates tissue degeneration, thus preserving salivation. Our data suggest that senescence in the salivary gland stem/progenitor cell niche contributes to radiation-induced hyposalivation. Pharmacological targeting of senescent cells may represent a therapeutic strategy to prevent radiotherapy-induced xerostomia.


2006 ◽  
Vol 37 (10) ◽  
pp. 955-959 ◽  
Author(s):  
F L Coracin ◽  
M E Pizzigatti Correa ◽  
E E Camargo ◽  
D E Peterson ◽  
A de Oliveira Santos ◽  
...  

iScience ◽  
2020 ◽  
Vol 23 (9) ◽  
pp. 101524
Author(s):  
Sangwon Min ◽  
Akinsola Oyelakin ◽  
Christian Gluck ◽  
Jonathan E. Bard ◽  
Eun-Ah Christine Song ◽  
...  

2006 ◽  
Vol 80 (8) ◽  
pp. 4200-4202 ◽  
Author(s):  
Xiuju Lu ◽  
Amelia K. Pinto ◽  
Ann M. Kelly ◽  
Kathy S. Cho ◽  
Ann B. Hill

ABSTRACT Compared to other organs, murine cytomegalovirus (MCMV) replication in the salivary gland is uniquely resistant to CD8 T-cell control. The contribution of viral genes that interfere with antigen presentation (VIPRs) to this resistance was assessed using a mutant lacking MCMV's known VIPRs. Salivary gland titers of the VIPR-deficient virus were at least 10-fold lower than those of the wild type during the persistent phase of infection; the defect was reversed by depleting CD8 T cells. Thus, VIPRs contribute to CD8 T cells' inability to control virus in the salivary gland.


2011 ◽  
Vol 17 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Adi Yaniv ◽  
Yoav Neumann ◽  
Ran David ◽  
Raluca Stiubea-Cohen ◽  
Yoav Orbach ◽  
...  

Author(s):  
D. E. Philpott ◽  
A. Takahashi

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.


Author(s):  
M.E. Cantino ◽  
M.K. Goddard ◽  
L.E. Wilkinson ◽  
D.E. Johnson

Quantification in biological x-ray microanalysis depends on accurate evaluation of mass loss. Although several studies have addressed the problem of electron beam induced mass loss from organic samples (eg., 1,2). uncertainty persists as to the dose dependence, the extent of loss, the elemental constituents affected, and the variation in loss for different materials and tissues. in the work described here, we used x-ray counting rate changes to measure mass loss in albumin (used as a quantification standard), salivary gland, and muscle.In order to measure mass loss at low doses (10-4 coul/cm2 ) large samples were needed. While freeze-dried salivary gland sections of the required dimensions were available, muscle sections of this size were difficult to obtain. To simulate large muscle sections, frog or rat muscle homogenate was injected between formvar films which were then stretched over slot grids and freeze-dried. Albumin samples were prepared by a similar procedure. using a solution of bovine serum albumin in water. Samples were irradiated in the STEM mode of a JEOL 100C.


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