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Cell Reports Feb 2022Insect salivary glands have been previously shown to function in pupal attachment and food lubrication by secreting factors into the lumen via an exocrine way. Here, we...
Insect salivary glands have been previously shown to function in pupal attachment and food lubrication by secreting factors into the lumen via an exocrine way. Here, we find in Drosophila that a salivary gland-derived secreted factor (Sgsf) peptide regulates systemic growth via an endocrine way. Sgsf is specifically expressed in salivary glands and secreted into the hemolymph. Sgsf knockout or salivary gland-specific Sgsf knockdown decrease the size of both the body and organs, phenocopying the effects of genetic ablation of salivary glands, while salivary gland-specific Sgsf overexpression increases their size. Sgsf promotes systemic growth by modulating the secretion of the insulin-like peptide Dilp2 from the brain insulin-producing cells (IPCs) and affecting mechanistic target of rapamycin (mTOR) signaling in the fat body. Altogether, our study demonstrates that Sgsf mediates the roles of salivary glands in Drosophila systemic growth, establishing an endocrine function of salivary glands.
Topics: Animals; Drosophila; Drosophila Proteins; Insulin; Peptides; Salivary Glands
PubMed: 35196492
DOI: 10.1016/j.celrep.2022.110397 -
Biochimica Et Biophysica Acta.... Nov 2018Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion... (Review)
Review
Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Saliva secretion is regulated by stimulation of specific signaling mechanisms within the acinar cells of the gland. Neurotransmitter-stimulated increase in cytosolic [Ca] ([Ca]) in acinar cells is the primary trigger for salivary fluid secretion from salivary glands, the loss of which is a critical factor underlying dry mouth conditions in patients. The increase in [Ca] regulates multiple ion channel and transport activities that together generate the osmotic gradient which drives fluid secretion across the apical membrane. Ca entry mediated by the Store-Operated Ca Entry (SOCE) mechanism provides the essential [Ca] signals to trigger salivary gland fluid secretion. Under physiological conditions depletion of ER-Ca stores is caused by activation of IP3R by IP3 and this provides the stimulus for SOCE. Core components of SOCE in salivary gland acinar cells are the plasma membrane Ca channels, Orai1 and TRPC1, and STIM1, a Ca-sensor protein in the ER, which regulates both channels. In addition, STIM2 likely enhances the sensitivity of cells to ER-Ca depletion thereby tuning the cellular response to agonist stimulation. Two major, clinically relevant, conditions which cause irreversible salivary gland dysfunction are radiation treatment for head-and-neck cancers and the autoimmune exocrinopathy, Sjögren's syndrome (pSS). However, the exact mechanism(s) that causes the loss of fluid secretion, in either condition, is not clearly understood. A number of recent studies have identified that defects in critical Ca signaling mechanisms underlie salivary gland dysfunction caused by radiation treatment or Sjögren's syndrome (pSS). This chapter will discuss these very interesting and important studies.
Topics: Acinar Cells; Animals; Calcium; Calcium Channels; Calcium Signaling; Disease Susceptibility; Humans; Intracellular Space; Neurotransmitter Agents; Saliva; Salivary Glands
PubMed: 30006140
DOI: 10.1016/j.bbamcr.2018.07.002 -
RNA Biology Dec 2017Epithelial-mesenchymal interactions are required to coordinate cell proliferation, patterning, and functional differentiation of multiple cell types in a developing... (Review)
Review
Epithelial-mesenchymal interactions are required to coordinate cell proliferation, patterning, and functional differentiation of multiple cell types in a developing organ. This exquisite coordination is dependent on various secreted molecules that provide developmental signals to mediate these tissue interactions. Recently, it was reported that mature mesenchymal-derived microRNAs (miRNAs) in the fetal mouse salivary gland are loaded into exosomes, and transported to the epithelium where they influence progenitor cell proliferation. The exosomal miRNAs regulated epithelial expression of genes involved in DNA methylation in progenitor cells to influence morphogenesis. Thus, exosomal miRNAs are mobile genetic signals that cross tissue boundaries within an organ. These findings raise many questions about how miRNA signals are initiated to coordinate organogenesis and whether they are master regulators of epithelial-mesenchymal interactions. The development of therapeutic applications using exosomal miRNAs for the regeneration of damaged adult organs is a promising area of research.
Topics: Animals; Biological Transport; Epithelial Cells; Epithelium; Exosomes; Extracellular Vesicles; Humans; Mesoderm; MicroRNAs; Molecular Diagnostic Techniques; Organogenesis; Salivary Glands; Signal Transduction
PubMed: 28816640
DOI: 10.1080/15476286.2017.1361098 -
Genesis (New York, N.Y. : 2000) May 2018Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by... (Review)
Review
Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by autoimmune diseases such as Sjögren's syndrome. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. However, these approaches have been hampered by a lack of knowledge on the identity of salivary stem cell populations and their regulators. In this review we discuss our current knowledge on salivary stem cells and their regulators during organ development, homeostasis and regeneration. As increasing evidence in other systems suggests that progenitor cells may be a source of cancer, we also review whether these same salivary stem cells may also be cancer initiating cells.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Humans; Neoplasms; Regeneration; Salivary Glands
PubMed: 29663717
DOI: 10.1002/dvg.23211 -
Blood Apr 2022
Topics: Humans; Lymphoma, B-Cell, Marginal Zone; Salivary Gland Neoplasms; Salivary Glands
PubMed: 35389438
DOI: 10.1182/blood.2021012624 -
Scientific Reports Jul 2023Novel modalities, such as salivary ultrasonography (SGUS) and shear wave elastography (SWE), have previously been introduced to evaluate Sjögren's syndrome (SS)....
Novel modalities, such as salivary ultrasonography (SGUS) and shear wave elastography (SWE), have previously been introduced to evaluate Sjögren's syndrome (SS). However, in secondary SS (sSS), the diagnostic performance of SGUS and its relationship with clinicopathological characteristics have not yet been clearly defined. In this study, we aimed to investigate sSS in RA patients using SGUS and SWE and sought to determine its pathological correlations. Thirty-one RA patients who presented with sicca symptoms were included to be evaluated on SS, and were compared with 18 primary SS (pSS) patients. All subjects were assessed through SGUS, SWE, and conventional diagnostic approaches for SS, including minor salivary gland biopsy (MSGB). In SGUS evaluation, two separate scoring systems, suggested by Hocevar and OMERACT, were used. Among 31 RA patients with sicca symptoms, 19 (61.2%) were diagnosed as sSS. Similar to pSS, SGUS showed good diagnostic performance (sensitivity 68.4% and 78.9%, and specificity 91.7% and 75.0% for Hocever and OMERACT, respectively) in differentiating sSS from RA patients with simple sicca symptoms. The sSS and pSS patients exhibited significantly higher lymphoid infiltration areas in MSGB than RA patients without SS. Focus score and lymphoid infiltration areas correlated well with sonographic severity. Severity of fibrosis in MSGB showed better positive correlation with SWE than with SGUS. Similar to pSS, SGUS shows good diagnostic performance for sSS in RA patients. SWE reflects histopathologic chronicity of MSGB well in both pSS and sSS.
Topics: Humans; Sjogren's Syndrome; Salivary Glands; Ultrasonography; Salivary Glands, Minor
PubMed: 37443200
DOI: 10.1038/s41598-023-38469-z -
Clinical and Experimental Rheumatology 2018Salivary gland ultrasonography (US) has recently been re-discovered as a useful tool to assess salivary gland involvement in primary Sjögren's syndrome (SS). In this... (Review)
Review
Salivary gland ultrasonography (US) has recently been re-discovered as a useful tool to assess salivary gland involvement in primary Sjögren's syndrome (SS). In this review, we discuss US of the major salivary glands in the diagnosis of primary SS and analyse the possible added value of inclusion in classification criteria. We review the literature concerning associations between US of the major salivary glands, salivary gland histology and serology, with the possibility that US may be of value in disease stratification. We also examine the possible utility for US to monitor patient response to therapy in both clinical research and standard clinical care.
Topics: Humans; Predictive Value of Tests; Prognosis; Reproducibility of Results; Salivary Glands; Severity of Illness Index; Sjogren's Syndrome; Ultrasonography
PubMed: 30296991
DOI: No ID Found -
Cancer Cytopathology Jan 2022
Topics: Humans; Japan; Salivary Gland Neoplasms; Salivary Glands
PubMed: 34478239
DOI: 10.1002/cncy.22506 -
Current Protocols in Cell Biology Jun 2019Organoids are important research tools for studying organ morphogenesis and differentiation because they recapitulate ex vivo the native 3D organization of cells that is...
Organoids are important research tools for studying organ morphogenesis and differentiation because they recapitulate ex vivo the native 3D organization of cells that is essential for proper cell and organ function. The composition of organoids can be manipulated to incorporate specific cell types to facilitate molecular interrogation of cell-cell interactions during organoid formation. A method for generating organoids derived from both embryonic salivary gland epithelial progenitor cells and mesenchymal support cells is described. Methods for isolating enriched populations of the epithelial cells as clusters and the mesenchyme cells as single cells from mouse embryonic submandibular salivary glands are also provided. Separating the epithelial and mesenchymal cell populations allows for independent molecular manipulation of each cell type. In addition, methods for lentiviral transduction of the mesenchyme cells and quantitative image analysis of organoids are provided. The methods described here are useful for exploring mechanisms driving organ formation. © 2018 by John Wiley & Sons, Inc.
Topics: Animals; Cell Lineage; Epithelial Cells; Mesoderm; Mice; Organoids; Salivary Glands; Tissue Culture Techniques
PubMed: 30394683
DOI: 10.1002/cpcb.76 -
The British Journal of Radiology Feb 2022Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease...
OBJECTIVE
Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease in salivary gland function.
METHODS
Salivary gland scintigraphy was performed to quantitatively evaluate the salivary gland functions in patients undergoing RT. It was done chronologically for 62 salivary glands of 31 patients before RT and retested 12 months later.
RESULTS
The salivary gland functions of most patients deteriorated post-RT and recovered when the radiation dose to the salivary gland was not high. The mean dose to the salivary gland was found to be the most reliable factor in deteriorating salivary gland function, and the tolerance dose was determined to be 46 Gy. The recovery rate of salivary gland function after 1 year of RT was 72% in the RT alone group ( = 10), 56% in the conformal radiotherapy group ( = 15), and 44% in the bioradiotherapy group ( = 6).
CONCLUSION
Scintigraphy revealed that the salivary glands recovered from post-RT hypofunction when decreased doses were administered. The determined tolerance dose of 46 Gy may guide the approach to minimizing associated xerostomia in RT.
ADVANCES IN KNOWLEDGE
In this study, the average tolerated dose to the salivary glands was 46 Gy.
Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Chemoradiotherapy; Cisplatin; Female; Head and Neck Neoplasms; Humans; Lymphatic Irradiation; Magnetic Resonance Imaging; Male; Middle Aged; Parotid Gland; Positron Emission Tomography Computed Tomography; Radiation Dosage; Radiation Tolerance; Radiation-Sensitizing Agents; Radiotherapy, Intensity-Modulated; Recovery of Function; Salivary Glands; Tomography, X-Ray Computed; Xerostomia
PubMed: 34928174
DOI: 10.1259/bjr.20210718