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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 -
International Journal of Molecular... Sep 2022Sjögren's syndrome is a chronic autoimmune disease characterized by systemic dysfunction of exocrine glands, mainly the salivary and lachrymal glands. Sjögren's... (Review)
Review
Sjögren's syndrome is a chronic autoimmune disease characterized by systemic dysfunction of exocrine glands, mainly the salivary and lachrymal glands. Sjögren's syndrome consists of two forms: primary Sjögren's syndrome, which is characterized by dry eyes and dry mouth without autoimmune diseases; and secondary Sjögren's syndrome, which is characterized by symptoms associated with other autoimmune diseases, such as systemic lupus erythematosus. Disease severities vary considerably from mild glandular dryness to severe glandular involvement with numerous extraglandular and systemic features. Sensorineural hearing loss is sometimes observed in both primary and secondary Sjögren's syndrome. This review article consists of (1) Pathology of Sjögren's syndrome, (2) Clinical manifestation of Sjögren's syndrome, (3) Autoimmune inner ear disease, (4) Histoanatomical features of the inner ear, (5) Immunological characteristics of the inner ear, (6) Pathophysiology of autoimmune inner ear disease, (7) Treatment for sensorineural hearing loss in Sjögren's syndrome, and (8) Future direction. Finally, we introduce a recently developed disease model of salivary gland inflammation and discuss future expectations for the treatment of sensorineural hearing loss in Sjögren's syndrome.
Topics: Exocrine Glands; Hearing Loss, Sensorineural; Humans; Keratoconjunctivitis Sicca; Labyrinth Diseases; Sjogren's Syndrome
PubMed: 36232483
DOI: 10.3390/ijms231911181 -
Development (Cambridge, England) Jul 2013Metazoans require epithelial and endothelial tubes to transport liquids and gasses throughout their bodies. Although biological tubes may look relatively similar at... (Review)
Review
Metazoans require epithelial and endothelial tubes to transport liquids and gasses throughout their bodies. Although biological tubes may look relatively similar at first glance, there are multiple and distinct mechanisms by which tubes form and even more regulatory events driving the cell shape changes that produce tubes of specific dimensions. An overview of the current understanding of the molecular processes and physical forces involved in tubulogenesis is presented in this review and the accompanying poster.
Topics: Animals; Blood Vessels; Endothelial Cells; Epithelial Cells; Exocrine Glands; Humans; Kidney Tubules; Lung; Morphogenesis
PubMed: 23821032
DOI: 10.1242/dev.070680 -
Cold Spring Harbor Perspectives in... May 2020Calcium (Ca) and cyclic AMP (cAMP) signaling cross talk and synergize to stimulate the cardinal functions of exocrine cells, regulated exocytosis, and fluid and... (Review)
Review
Calcium (Ca) and cyclic AMP (cAMP) signaling cross talk and synergize to stimulate the cardinal functions of exocrine cells, regulated exocytosis, and fluid and electrolyte secretion. This physiological process requires the organization of the two signaling pathways into complexes at defined cellular domains and close placement. Such domains are formed by membrane contact sites (MCS). This review discusses the basic properties of Ca signaling in exocrine cells, the role of MCS in the organization of cell signaling and in cross talk and synergism between the Ca and cAMP signaling pathways and, finally, the mechanism by which the Ca and cAMP pathways synergize to stimulate epithelial fluid and electrolyte secretion.
Topics: Animals; Calcium; Calcium Signaling; Cyclic AMP; Cytoplasm; Electrolytes; Endoplasmic Reticulum; Epithelial Cells; Exocrine Glands; Exocytosis; Humans; Protein Domains; Signal Transduction
PubMed: 31636079
DOI: 10.1101/cshperspect.a035279 -
Reviews in Endocrine & Metabolic... Jun 2021The mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly... (Review)
Review
The mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. Among the features that make the MG unique there are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure MG's proper development at puberty and remodeling during the lactation cycle. Although MG adipocytes play such a critical role for the gland development, most of the studies have focused on its epithelial component only, leaving the role of the neighboring adipocytes largely unexplored. In this review we aim to describe evidences regarding MG's adipocytes role and properties in physiologic conditions (gland development and lactation cycle), obesity and breast cancer, emphasizing the existing gaps in the literature which deserve further investigation.
Topics: Adipocytes; Animals; Breast Neoplasms; Female; Humans; Lactation; Mammary Glands, Animal; Mammary Glands, Human; Obesity; Pregnancy
PubMed: 33751362
DOI: 10.1007/s11154-021-09633-5 -
International Journal of Molecular... Jul 2023Sjögren's syndrome (SS) is an autoimmune disease characterized by the involvement of exocrine glands such as the salivary and lacrimal glands. The minor salivary... (Review)
Review
Sjögren's syndrome (SS) is an autoimmune disease characterized by the involvement of exocrine glands such as the salivary and lacrimal glands. The minor salivary glands, from which tissue samples may be obtained, are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of SS. In the onset of SS, autoantigens derived from the salivary glands are recognized by antigen-presenting dendritic cells, leading to the activation of T and B cells, cytokine production, autoantibody production by plasma cells, the formation of ectopic germinal centers, and the destruction of salivary gland epithelial cells. A recent therapeutic approach with immune checkpoint inhibitors for malignant tumors enhances the anti-tumor activity of cytotoxic effector T cells, but also induces SS-like autoimmune disease as an adverse event. In the treatment of xerostomia, muscarinic agonists and salivary gland duct cleansing procedure, as well as sialendoscopy, are expected to ameliorate symptoms. Clinical trials on biological therapy to attenuate the hyperresponsiveness of B cells in SS patients with systemic organ involvement have progressed. The efficacy of treatment with mesenchymal stem cells and chimeric antigen receptor T cells for SS has also been investigated. In this review, we will provide an overview of the pathogenesis of salivary gland lesions and recent trends in therapeutic approaches for SS.
Topics: Humans; Sjogren's Syndrome; Xerostomia; Salivary Glands, Minor; Germinal Center; Salivary Ducts
PubMed: 37446355
DOI: 10.3390/ijms241311179 -
Frontiers in Endocrinology 2020Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide widely distributed in the nervous system, where it exerts strong neuroprotective effects.... (Review)
Review
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide widely distributed in the nervous system, where it exerts strong neuroprotective effects. PACAP is also expressed in peripheral organs but its peripheral protective effects have not been summarized so far. Therefore, the aim of the present paper is to review the existing literature regarding the cytoprotective effects of PACAP in non-neuronal cell types, peripheral tissues, and organs. Among others, PACAP has widespread expression in the digestive system, where it shows protective effects in various intestinal pathologies, such as duodenal ulcer, small bowel ischemia, and intestinal inflammation. PACAP is present in both the exocrine and endocrine pancreas as well as liver where it reduces inflammation and steatosis by interfering with hepatic pathology related to obesity. It is found in several exocrine glands and also in urinary organs, where, with its protective effects being mainly published regarding renal pathologies, PACAP is protective in numerous conditions. PACAP displays anti-inflammatory effects in upper and lower airways of the respiratory system. In the skin, it is involved in the development of inflammatory pathology such as psoriasis and also has anti-allergic effects in a model of contact dermatitis. In the non-neuronal part of the visual system, PACAP showed protective effects in pathological conditions of the cornea and retinal pigment epithelial cells. The positive role of PACAP has been demonstrated on the formation and healing processes of cartilage and bone where it also prevents osteoarthritis and rheumatoid arthritis development. The protective role of PACAP was also demonstrated in the cardiovascular system in different pathological processes including hyperglycaemia-induced endothelial dysfunction and age-related vascular changes. In the heart, PACAP protects against ischemia, oxidative stress, and cardiomyopathies. PACAP is also involved in the protection against the development of pre-senile systemic amyloidosis, which is presented in various peripheral organs in PACAP-deficient mice. The studies summarized here provide strong evidence for the cytoprotective effects of the peptide. The survival-promoting effects of PACAP depend on a number of factors which are also shortly discussed in the present review.
Topics: Animals; Cardiovascular System; Digestive System; Exocrine Glands; Fatty Liver; Humans; Inflammation; Pancreas, Exocrine; Pituitary Adenylate Cyclase-Activating Polypeptide; Respiratory System; Skin; Urogenital System
PubMed: 32765418
DOI: 10.3389/fendo.2020.00377 -
Archivum Immunologiae Et Therapiae... Dec 2017Amphiregulin (AREG) is a well-characterized member of the epidermal growth factor (EGF) family and is one of the ligands of the EGF receptor (EGFR). AREG plays a key... (Review)
Review
Amphiregulin (AREG) is a well-characterized member of the epidermal growth factor (EGF) family and is one of the ligands of the EGF receptor (EGFR). AREG plays a key role in mammalian development and in the control of branching morphogenesis in various organs. Furthermore, AREG participates in a wide range of physiological and pathological processes activating the major intracellular signalling cascades governing cell survival, proliferation and motility. In this article, we review current advances in exocrine glands morphogenesis, focusing on the salivary gland, and discuss the essential aspects of AREG structure, function and regulation, and its differential role within the EGFR family of ligands. Finally, we identify emerging aspects in AREG research applied to mammary gland development and the salivary gland autoimmune disease, Sjögren's syndrome.
Topics: Amphiregulin; Animals; Epidermal Growth Factor; Epithelial Cells; Exocrine Glands; Fibroblasts; Gene Expression Regulation, Developmental; Humans; Morphogenesis; Salivary Glands; Signal Transduction; Sjogren's Syndrome
PubMed: 28593345
DOI: 10.1007/s00005-017-0478-2 -
Cell Calcium Jun 2014In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function,... (Review)
Review
In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca(2+)-dependent K(+) channels take part in key functions including membrane potential regulation, fluid movement and K(+) secretion in exocrine glands. Two K(+) channels have been identified in exocrine salivary glands: (1) a Ca(2+)-activated K(+) channel of intermediate single channel conductance encoded by the KCNN4 gene, and (2) a voltage- and Ca(2+)-dependent K(+) channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca(2+)-dependent K(+) channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca(2+)-dependent K(+) channels by protein-protein interactions that may significantly impact exocrine gland physiology.
Topics: Acinar Cells; Calcium; Humans; Intermediate-Conductance Calcium-Activated Potassium Channels; Potassium; Protein Interaction Domains and Motifs; Salivary Glands
PubMed: 24559652
DOI: 10.1016/j.ceca.2014.01.005