-
Physiological Reviews Jul 2022Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological... (Review)
Review
Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.
Topics: Cell Lineage; Humans; Oral Health; Regeneration; Salivary Glands; Signal Transduction
PubMed: 35343828
DOI: 10.1152/physrev.00015.2021 -
Dental Clinics of North America Jan 2020A variety of diseases ranging from obstructions, infections, to benign and malignant tumors occur in salivary glands. The most common problem is painful blockage of... (Review)
Review
A variety of diseases ranging from obstructions, infections, to benign and malignant tumors occur in salivary glands. The most common problem is painful blockage of ducts by stones that prevents drainage of saliva. Sialadenitis can be due to either infectious or noninfectious factors. Bacterial or viral infections are the most common causes of acute sialadenitis. Staphylococcus is the usual bacterial cause, whereas paramyxovirus (mumps) is the common viral cause. Eighty percent of salivary tumors are benign, whereas about 20% are malignant. Most tumors occur in the parotid gland and on the hard palate. Classifications, imaging, and suggested treatment are described.
Topics: Humans; Salivary Gland Diseases; Salivary Gland Neoplasms; Salivary Glands; Sialadenitis; Virus Diseases
PubMed: 31735235
DOI: 10.1016/j.cden.2019.08.007 -
Cells Aug 2019Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune diseases, infections and physical traumas, can alter the... (Review)
Review
Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune diseases, infections and physical traumas, can alter the functionality of these glands, greatly impacting the quality of life of patients. To date, no definitive therapeutic approach can compensate the impairment of salivary glands, and treatment are purely symptomatic. Understanding the cellular and molecular control of salivary glands function is, therefore, highly relevant for therapeutic purposes. In this review, we provide a starting platform for future studies in basic biology and clinical research, reporting classical ideas on salivary gland physiology and recently developed technology to guide regeneration, reconstruction and substitution of the functional organs.
Topics: Animals; Female; Gene Regulatory Networks; Humans; Male; Mice; Regeneration; Salivary Glands; Sex Characteristics; Species Specificity
PubMed: 31455013
DOI: 10.3390/cells8090976 -
Nature Reviews. Rheumatology Jun 2021In primary Sjögren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the... (Review)
Review
In primary Sjögren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-κB pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4 T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS.
Topics: B-Lymphocytes; CD4-Positive T-Lymphocytes; Epithelial Cells; Humans; Immune Checkpoint Inhibitors; Inflammasomes; Interferons; Lymphoma, B-Cell, Marginal Zone; NF-kappa B; Salivary Glands; Sjogren's Syndrome
PubMed: 33911236
DOI: 10.1038/s41584-021-00605-2 -
Cell Jul 2021Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of...
Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of stratified epithelia, such as in the embryonic salivary gland and pancreas. Here, we performed live-organ imaging of mouse embryonic salivary glands at single-cell resolution to reveal that budding morphogenesis is driven by expansion and folding of a distinct epithelial surface cell sheet characterized by strong cell-matrix adhesions and weak cell-cell adhesions. Profiling of single-cell transcriptomes of this epithelium revealed spatial patterns of transcription underlying these cell adhesion differences. We then synthetically reconstituted budding morphogenesis by experimentally suppressing E-cadherin expression and inducing basement membrane formation in 3D spheroid cultures of engineered cells, which required β1-integrin-mediated cell-matrix adhesion for successful budding. Thus, stratified epithelial budding, the key first step of branching morphogenesis, is driven by an overall combination of strong cell-matrix adhesion and weak cell-cell adhesion by peripheral epithelial cells.
Topics: Animals; Basement Membrane; Cell Adhesion; Cell Division; Cell Movement; Cell Tracking; Cell-Matrix Junctions; Embryo, Mammalian; Epithelial Cells; Epithelium; Gene Expression Regulation, Developmental; HEK293 Cells; Humans; Integrins; Mice; Models, Biological; Morphogenesis; Salivary Glands; Transcriptome
PubMed: 34133940
DOI: 10.1016/j.cell.2021.05.015 -
Radiotherapy and Oncology : Journal of... Jan 2021The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission...
INTRODUCTION
The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy.
MATERIALS AND METHODS
The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated.
RESULTS
All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated post-treatment xerostomia and dysphagia ≥ grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p = .007; 0.016/gy, 95%CI 0.001-0.031, p = .036). Follow-up at 24 months had similar results.
CONCLUSION
The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life.
Topics: Head and Neck Neoplasms; Humans; Male; Parotid Gland; Positron Emission Tomography Computed Tomography; Quality of Life; Radiotherapy, Conformal; Retrospective Studies; Salivary Glands; Xerostomia
PubMed: 32976871
DOI: 10.1016/j.radonc.2020.09.034 -
Frontiers in Immunology 2022Primary Sjogren's syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It...
BACKGROUND
Primary Sjogren's syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown.
METHODS
The mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease.
RESULTS
The bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, , , , and , were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (, , and ) and fusion (, , and ) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells.
CONCLUSION
Our study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function.
Topics: Gene Expression Profiling; Humans; Mitochondria; Salivary Glands; Salivary Glands, Minor; Sjogren's Syndrome
PubMed: 35359935
DOI: 10.3389/fimmu.2022.845209 -
Oral Radiology Apr 2023Non-tumour inflammatory and obstructive salivary gland pathologies such as sialadenitis, sialolithiasis, sialadenosis, ductal strictures, etc. require precise... (Review)
Review
Non-tumour inflammatory and obstructive salivary gland pathologies such as sialadenitis, sialolithiasis, sialadenosis, ductal strictures, etc. require precise radiological evaluation and mapping of salivary gland ductal system for better treatment outcome. Conventional sialography is considered as a useful and reliable technique in evaluation of salivary glands especially intrinsic and acquired abnormalities involving the ductal system and is useful for detection of non-radiopaque sialoliths which are invisible on routine plain radiographs. Primarily sialography is used as a diagnostic tool, additionally it plays an important therapeutic role as salivary gland lavage in cases of recurrent salivary gland infections and in obstructive salivary gland disorders by helping in clearance of mucous plugs or small sialoliths within the ducts. Recently, diagnostic performance of computed tomography (CT) sialography is being explored and has been reported to have high sensitivity in detection of small sialoliths and allows differentiation of sialoliths from other calcifications in glandular ductal system. Multiplanar three dimensional (3D) reconstructed CT images have been reported to play a key role in determination of anatomical location or extent of salivary gland disease without superimposition or distortion of structures. This review aims to discuss the disease specific applications of sialography and CT Sialography in particular for visualization of salivary gland disorders.
Topics: Humans; Sialography; Salivary Gland Calculi; Salivary Gland Diseases; Salivary Glands; Sialadenitis
PubMed: 36562930
DOI: 10.1007/s11282-022-00668-1 -
Oral and Maxillofacial Surgery Clinics... Aug 2021Although a rare sequala of soft tissue injury, salivary gland trauma may result in significant morbidity. Salivary gland injury can involve the major as well as the... (Review)
Review
Although a rare sequala of soft tissue injury, salivary gland trauma may result in significant morbidity. Salivary gland injury can involve the major as well as the minor glands. Because of the proximity of adjacent vital structures, a thorough history and physical examination are mandatory during patient evaluation. Trauma to the major salivary glands may involve the parenchyma, duct, or neural injury. Treatment requires adherence to primary principles of soft tissue management. Ductal and neural injury should be repaired primarily. Sialocele and fistula are potential complications of repaired and unrepaired salivary gland injury.
Topics: Humans; Parotid Gland; Salivary Gland Diseases; Salivary Glands
PubMed: 34116909
DOI: 10.1016/j.coms.2021.04.008 -
European Journal of Pharmaceutics and... Sep 2019Saliva is a multifaceted bodily fluid that is often taken for granted but is indispensable for oral health and overall well-being in humans. Although mainly comprised of... (Review)
Review
Saliva is a multifaceted bodily fluid that is often taken for granted but is indispensable for oral health and overall well-being in humans. Although mainly comprised of water (99.5%), proteins, ions and enzymes turn saliva into a viscoelastic solution that performs a variety of vital tasks. This review article gives a brief overview of the salivary gland system, as well as the composition, output and functions of saliva. It also addresses the current applications of saliva for diagnostic purposes, the clinical relevance of saliva in oral diseases as well as current treatment options.
Topics: Body Fluids; Humans; Mouth Diseases; Oral Health; Saliva; Salivary Glands
PubMed: 31220573
DOI: 10.1016/j.ejpb.2019.06.016