Salivary gland function, development, and regeneration

Chibly, Alejandro M.; Aure, Marit H.; Patel, Vaishali; Hoffman, Matthew P.

doi:10.1152/physrev.00015.2021

Cited by 64 publications

(53 citation statements)

References 610 publications

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“…9B). Upon removal of the ligation followed by 14 days of regeneration (regenerated), acinar cells were replaced regardless of the extent of injury, however, there was a slower reappearance of acinar cells upon severe injury as previously described 13,19,38] (Supplementary Fig. 9B).…”

Section: δNp63 Is Dispensable For Mec Ability To Respond During Smg R...supporting

confidence: 60%

ΔNp63 maintains the fidelity of the myoepithelial cell lineage and directs cell differentiation programs in the murine salivary gland

et al. 2022

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Salivary glands consist of several epithelial cell types of distinct lineages and functional characteristics that are established by directed differentiation programs of resident stem and progenitor cells. We have shown that ΔNp63, a crucial transcriptional regulator of stem/progenitor cells, is enriched in both the basal and myoepithelial cell (MEC) populations and that ΔNp63 positive cells maintain all the descendent epithelial cell lineages of the adult mouse salivary glands (mSGs). Although this pivotal role of ΔNp63 in driving the broader epithelial cell fate and identity in the mSG has been demonstrated, how ΔNp63 functions specifically in the commitment and differentiation of the MEC population is less understood. Using multiple genetic mouse models that allow for cell tracing, we show that ΔNp63 is critical in maintaining and renewing MECs, in part through the transcriptional regulation of Acta2 gene expression, a defining marker of this cell population. We demonstrate that during adult mSG homeostasis, ΔNp63 enriched MECs function as bipotent progenitor cells that maintain not only the MEC population, but also the distinctly different ductal cell lineages. The fidelity of this process is dependent on ΔNp63 expression, since MEC-specific ablation of ΔNp63 results in altered MEC differentiation and affects cellular plasticity resulting in aberrant differentiation of the intercalated ducts and acinar cells. In contrast, we find that the contribution of MECs to ductal and acinar cell regeneration following severe injury is independent of ΔNp63. Our observations offer new insights into cellular mechanisms driving MEC fate choices and differentiation programs in the context of salivary gland homeostasis and in response to injury and regeneration. Long term, these findings have implications for better treatment of salivary gland dysfunction through stem cell-based approaches.

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Section: δNp63 Is Dispensable For Mec Ability To Respond During Smg R...supporting

confidence: 60%

ΔNp63 maintains the fidelity of the myoepithelial cell lineage and directs cell differentiation programs in the murine salivary gland

et al. 2022

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Section: Unidirectional Movement Of Fluid In the Salivary Glandsmentioning

confidence: 99%

“…Most of the secretion from the PAR glands occurs in response to stimuli, while the SM and SL glands are responsible for the majority of unstimulated saliva production [ 22 ]. These glands differ in the types of secretion they produce: the PAR glands produce a serous, watery secretion; the SM glands produce a mixed serous and mucous secretion; and the SL glands secrete saliva that is predominantly mucous in character [ 22 ]. One striking example of a gland-specific expression is salivary amylase, which shows abundant expression at the protein level in the PAR and SM glandular tissue while being virtually absent in the SL glands [ 23 ].…”

Section: Unidirectional Movement Of Fluid In the Salivary Glandsmentioning

confidence: 99%

Xerostomia and Its Cellular Targets

Kim

2023

IJMS

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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.

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“…When a person is at rest, the submandibular gland is responsible for the majority of saliva production [ 22 ]. The parotid gland and the sublingual gland are only responsible for producing about 20% and 8% of saliva, respectively; however, when the production of saliva is stimulated, for example, by sodium chloride or by acid stimulation, the majority of generated saliva originates predominantly from the parotid gland [ 23 ]. Therefore, whether to stimulate, as well as stimulating substances and the degree of stimulation, should also be considered.…”

Section: Introductionmentioning

confidence: 99%

Obtaining a Reliable Diagnostic Biomarker for Diabetes Mellitus by Standardizing Salivary Glucose Measurements

et al. 2022

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Salivary glucose is frequently utilized in diabetes mellitus (DM), and it might be proposed as a potential biomarker candidate for DM, as it is non-invasive and cost-effective and achieves adequate diagnostic performance for DM patients. However, salivary glucose levels may change under specific conditions. It is consequently essential to maintain a consistent strategy for measuring saliva, taking into account the possibility of external factors influencing salivary glucose levels. In this study, we analyzed salivary glucose levels under different handling conditions and donor-dependent factors, including age, interdiurnal variations, and collection and processing methods. A structured questionnaire was used to determine the symptoms and predisposing factors of DM. The glucose oxidase peroxidase method was used to estimate glucose levels in the blood and saliva of people in a fasting state. The aim of this study is to investigate the effect of such conditions on salivary glucose levels. We found that these extraneous variables should be taken into account in the future when salivary glucose is used as a predictive biomarker for DM.

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Salivary gland function, development, and regeneration

Cited by 64 publications

References 610 publications

ΔNp63 maintains the fidelity of the myoepithelial cell lineage and directs cell differentiation programs in the murine salivary gland

ΔNp63 maintains the fidelity of the myoepithelial cell lineage and directs cell differentiation programs in the murine salivary gland

Xerostomia and Its Cellular Targets

Obtaining a Reliable Diagnostic Biomarker for Diabetes Mellitus by Standardizing Salivary Glucose Measurements

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