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Recent Advances in Salivary Gland and Their Function 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 9851

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Prof. Dr. Sang-Gun Ahn

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Department of Pathology, School of Dentistry, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea
Interests: cellular stress defense mechanism; aging and metabolism; photodynamic therapy in cancer
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Dear Colleagues,

Salivary gland dysfunctional changes occur with reduced salivary flow and dry mouth (xerostomia) and commonly involve oral dysfunction, tooth structure deterioration, and infection through reduced salivation. Anatomically, aging induces atrophy of acinar cells (ACs) and replacement of normal gland parenchyma with adipose tissue, connective tissue, and oncocytes. Recently, numerous medical drugs and treatments (radiation, chemotherapy) have been shown to significantly contribute to salivary gland dysfunction. Although changes associated with salivary gland dysfunction are affected by multiple factors, such as the environment, not all changes are considered to be physiological, and how aging influences the function of salivary glands is unclear.

This Special Issue discusses the mechanism of aging–salivary gland disorder, and new entities, such as functional regeneration of the salivary gland. Furthermore, we provide an overview of new advances in the diagnostic, prognostic, and therapeutic implications of aging and the salivary gland.

Prof. Dr. Sang-Gun Ahn
Guest Editor

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Keywords

salivary gland
aging
oral dysfunction
functional regeneration
metabolism

Published Papers (4 papers)

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Research

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41 pages, 1260 KiB

Open AccessArticle

A Catalog of Coding Sequence Variations in Salivary Proteins’ Genes Occurring during Recent Human Evolution

by Lorena Di Pietro, Mozhgan Boroumand, Wanda Lattanzi, Barbara Manconi, Martina Salvati, Tiziana Cabras, Alessandra Olianas, Laura Flore, Simone Serrao, Carla M. Calò, Paolo Francalacci, Ornella Parolini and Massimo Castagnola

Int. J. Mol. Sci. 2023, 24(19), 15010; https://doi.org/10.3390/ijms241915010 - 9 Oct 2023

Cited by 1 | Viewed by 1178

Abstract

Saliva houses over 2000 proteins and peptides with poorly clarified functions, including proline-rich proteins, statherin, P-B peptides, histatins, cystatins, and amylases. Their genes are poorly conserved across related species, reflecting an evolutionary adaptation. We searched the nucleotide substitutions fixed in these salivary proteins’ gene loci in modern humans compared with ancient hominins. We mapped 3472 sequence variants/nucleotide substitutions in coding, noncoding, and 5′-3′ untranslated regions. Despite most of the detected variations being within noncoding regions, the frequency of coding variations was far higher than the general rate found throughout the genome. Among the various missense substitutions, specific substitutions detected in PRB1 and PRB2 genes were responsible for the introduction/abrogation of consensus sequences recognized by convertase enzymes that cleave the protein precursors. Overall, these changes that occurred during the recent human evolution might have generated novel functional features and/or different expression ratios among the various components of the salivary proteome. This may have influenced the homeostasis of the oral cavity environment, possibly conditioning the eating habits of modern humans. However, fixed nucleotide changes in modern humans represented only 7.3% of all the substitutions reported in this study, and no signs of evolutionary pressure or adaptative introgression from archaic hominins were found on the tested genes. Full article

(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function 2.0)

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21 pages, 5787 KiB

Open AccessArticle

Peroxisomes Are Highly Abundant and Heterogeneous in Human Parotid Glands

by Christoph Watermann, Malin Tordis Meyer, Steffen Wagner, Claus Wittekindt, Jens Peter Klussmann, Sueleyman Erguen, Eveline Baumgart-Vogt and Srikanth Karnati

Int. J. Mol. Sci. 2023, 24(5), 4783; https://doi.org/10.3390/ijms24054783 - 1 Mar 2023

Cited by 2 | Viewed by 1578

Abstract

The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland’s striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue. Full article

(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function 2.0)

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14 pages, 4583 KiB

Open AccessArticle

CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target

by Marcel Mayer, Lisa Nachtsheim, Franziska Hoffmann, Ferdinand von Eggeling, Orlando Guntinas-Lichius, Johanna Prinz, Jens Peter Klußmann, Alexander Quaas, Christoph Arolt and Philipp Wolber

Int. J. Mol. Sci. 2022, 23(16), 9037; https://doi.org/10.3390/ijms23169037 - 12 Aug 2022

Cited by 2 | Viewed by 2260

Abstract

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman’s ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs. Full article

(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function 2.0)

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Review

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15 pages, 991 KiB

Open AccessReview

Xerostomia and Its Cellular Targets

by Yoon-Jung Kim

Int. J. Mol. Sci. 2023, 24(6), 5358; https://doi.org/10.3390/ijms24065358 - 10 Mar 2023

Cited by 6 | Viewed by 4166

Abstract

Xerostomia, the subjective feeling of a dry mouth associated with dysfunction of the salivary glands, is mainly caused by radiation and chemotherapy, various systemic and autoimmune diseases, and drugs. As saliva plays numerous essential roles in oral and systemic health, xerostomia significantly reduces quality of life, but its prevalence is increasing. Salivation mainly depends on parasympathetic and sympathetic nerves, and the salivary glands responsible for this secretion move fluid unidirectionally through structural features such as the polarity of acinar cells. Saliva secretion is initiated by the binding of released neurotransmitters from nerves to specific G-protein-coupled receptors (GPCRs) on acinar cells. This signal induces two intracellular calcium (Ca²⁺) pathways (Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx across the plasma membrane), and this increased intracellular Ca²⁺ concentration ([Ca²⁺]_i) causes the translocation of the water channel aquaporin 5 (AQP5) to the apical membrane. Consequently, the GPCR-mediated increased [Ca²⁺]_i in acinar cells promotes saliva secretion, and this saliva moves into the oral cavity through the ducts. In this review, we seek to elucidate the potential of GPCRs, the inositol 1,4,5-trisphosphate receptor (IP₃R), store-operated Ca²⁺ entry (SOCE), and AQP5, which are essential for salivation, as cellular targets in the etiology of xerostomia. Full article

(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function 2.0)

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