The role of the epithelial-to-mesenchymal transition (EMT) in diseases of the salivary glands

Sisto, Margherita; Lisi, Sabrina; Ribatti, Doménico

doi:10.1007/s00418-018-1680-y

Cited by 30 publications

(32 citation statements)

References 181 publications

(210 reference statements)

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“…Recently, the expression of CEACAM1 was shown to positively correlate with the expression of factors that are related to epithelial-mesenchymal transition (EMT) (Yoshikawa et al 2017). During pathological fibrosis following radiation therapy, healthy salivary acinar cells undergo a partial EMT and differentiate into a fibroblast-like phenotype (Hall et al 2010;Sisto et al 2018). Therefore, the extension of CEACAM1 membrane localization to the basal side of surviving acinar epithelial cells could indicate, on the one hand, an increased interaction of these cells with the extracellular matrix (ECM) but on the other hand also an EMT process induced by IR.…”

Section: Discussionmentioning

confidence: 99%

Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irradiation

et al. 2020

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Salivary gland (SG) hypofunction is a common post-radiotherapy complication. Besides the parenchymal damage after irradiation (IR), there are also effects on mesenchymal stem cells (MSCs) which were shown to contribute to regeneration and repair of damaged tissues by differentiating into stromal cell types or releasing vesicles and soluble factors supporting the healing processes. However, there are no adequate reports about their roles during SG damage and regeneration so far. Using an irradiated SG mouse model, we performed certain immunostainings on tissue sections of submandibular glands at different time points after IR. Immunostaining for CD31 revealed that already one day after IR, vascular impairment was induced at the level of capillaries. In addition, the expression of CD44—a marker of acinar cells—diminished gradually after IR and, by 20 weeks, almost disappeared. In contrast, the number of CD34-positive cells significantly increased 4 weeks after IR and some of the CD34-positive cells were found to reside within the adventitia of arteries and veins. Laser confocal microscopic analyses revealed an accumulation of CD34-positive cells within the area of damaged capillaries where they were in close contact to the CD31-positive endothelial cells. At 4 weeks after IR, a fraction of the CD34-positive cells underwent differentiation into α-SMA-positive cells, which suggests that they may contribute to regeneration of smooth muscle cells and/or pericytes covering the small vessels from the outside. In conclusion, SG-resident CD34-positive cells represent a population of progenitors that could contribute to new vessel formation and/or remodeling of the pre-existing vessels after IR and thus, might be an important player during SG tissue healing.

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Section: Discussionmentioning

confidence: 99%

Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irradiation

et al. 2020

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“…In this study we detected the expression level of P-mTOR in salivary glands from embryonic stage to ICR mice at P1stage (Figs 1E and 9G). In the progression of salivary gland carcinoma, activation of mTOR, AKT and epithelial-to-mesenchymal transition (EMT) were seen in adult humans [66][67][68][69]. This phenomenon is similar to the activation of mTOR and AKT (Fig.…”

Section: Discussionmentioning

confidence: 59%

“…However, there was only a 50% decrease in the expression level of P-mTOR, and P-S6K1 was not detected. In the progression of salivary gland carcinoma, activation of mTOR, AKT and epithelial-to-mesenchymal transition (EMT) were seen in adult humans [66][67][68][69]. This result showed that rapamycin selectively inhibits the mTORC1 signalling pathways without affecting mTORC2 during in vivo salivary gland development.…”

Section: Discussionmentioning

confidence: 92%

Role of the mTOR signalling pathway in salivary gland development

et al. 2019

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Development of the salivary gland is characterized by extensive branching morphogenesis. Although various molecules have been implicated in salivary gland development, the role of the mammalian target of rapamycin (mTOR) signalling pathway, including both mTOR complexes 1 and 2 (mTORC1 and 2), in salivary gland development is unknown. Here, we examined protein expression levels related to the mTOR signalling pathway using an ex vivo submandibular salivary gland (SMG) organ culture. We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E‐binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). In addition, AKT, which is an upstream protein kinase of mTORC1 and is downstream of mTORC2, is inhibited by LY294002 (a phosphatidylinositol 3‐kinase inhibitor), but not by rapamycin. Moreover, rapamycin‐treated ICR neonatal mice exhibited a reduction in both body weight and salivary glands compared with vehicle‐treated neonatal mice. The present data indicate that the mTOR signalling pathway, including both mTORC1 and mTORC2, plays a critical role in salivary gland development both in ex vivo SMG organ culture and ICR neonatal mice in vivo.

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“…A previous study reported that ongoing EMT may result in the progression of numerous diseases, such as cancer ( 36 ) and chronic kidney disease ( 37 ), particularly in CRSwNP ( 1 ). Following injury, the expression of junctional proteins, including E-cadherin, are downregulated and the expression of mesenchymal proteins, such as α-SMA, vimentin and fibronectin, are upregulated in epithelial cells, which then undergo EMT and alter morphology ( 38 ). In accordance with previous studies, the present study suggested that E-cadherin expression was reduced, while expression of α-SMA, vimentin and fibronectin were increased in CRSwNP and CRSsNP tissues compared with control groups.…”

Section: Discussionmentioning

confidence: 99%

miR‑155‑5p downregulation inhibits epithelial‑to‑mesenchymal transition by targeting SIRT1 in human nasal epithelial cells

et al. 2020

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epithelial-to-mesenchymal transition (eMT) in nasal epithelial cells is involved with tissue remodeling of nasal polyps. The present study investigated the molecular mechanisms through which mir-155-5p regulated eMT in chronic rhinosinusitis (crS). Patients were divided into the following groups: crSsnP, crS without nasal polyposis group, crSwnP, crS with nasal polyposis and controls. The expression of transforming growth factor (TGF)-β1, eMT markers, sirtuin 1 (SirT1) and mir-155-5p were determined by western blotting and reverse transcription-quantitative Pcr. cell morphology following TGF-β1 treatment in the presence of mir-155-5p inhibitors or controls was observed under a microscope. Target genes and potential binding sites between mir-155-5p and SirT1 were predicted by TargetScan and confirmed using dual-luciferase reporter assay. In patients with crS, the expression levels of e-cadherin were downregulated and the expression levels of TGF-β1, mesenchymal markers and mir-155-5p were upregulated. additionally, these changes in expression levels were reduced or increased to a greater extent in the crSwnP group compared with the crSsnP group. Furthermore, TGF-β1 expression promoted eMT in human nasal epithelial cells (Hnepcs) and upregulated mir-155-5p expression. These effects were reversed by mir-155-5p inhibitors. additionally, SirT1 was predicted as a target gene of mir-155-5p. downregulation of mir-155-5p upregulated epithelial marker expression and downregulated mesenchymal marker expression by regulating SirT1. Therefore, the downregulation of mir-155-5p inhibited eMT in Hnepcs by targeting SirT1.

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The role of the epithelial-to-mesenchymal transition (EMT) in diseases of the salivary glands

Cited by 30 publications

References 181 publications

Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irradiation

Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irradiation

Role of the mTOR signalling pathway in salivary gland development

miR‑155‑5p downregulation inhibits epithelial‑to‑mesenchymal transition by targeting SIRT1 in human nasal epithelial cells

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