Aquaporins in Salivary Glands: From Basic Research to Clinical Applications

Delporte, Christine; Bryla, Angélic; Perret, Jason

doi:10.3390/ijms17020166

Cited by 70 publications

(68 citation statements)

References 120 publications

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“…Therefore, characterization of aquaporins is mostly referred to mouse, rat, or human salivary glands, but a thorough characterization for the human oral mucosa is still missing. 70 In our oral mucosa model, we demonstrated the expression of AQP1, AQP3, AQP6, AQP7, AQP9, AQP10, and AQP11. The biopsy samples of the human oral mucosa showed a similar expression pattern as our model.…”

Section: Discussionmentioning

confidence: 72%

Optimization of an oral mucosa in vitro model based on cell line TR146

et al. 2020

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During the last years, the popularity of saliva has been increasing for its applicability as a diagnostic fluid. Blood biomarker molecules have to cross the blood-saliva barrier (BSB) in order to appear in saliva. The BSB consists of all oral and salivary gland epithelial barriers. Within this context, the optimization of in vitro models for mechanistic studies about the transport of molecules across the oral mucosa is an important task. Here, we describe the optimization and comprehensive characterization of a Transwell model of the oral mucosa based on the epithelial cell line TR146. Through systematic media optimization investigating 12 different setups , a significant increase of barrier integrity upon airlift cultivation was achieved for TR146 cell layers. The distinct improvement of the paracellular barrier was shown by measurements of transepithelial electrical resistance (TEER) and carboxyfluorescein permeability assays. Histological characterization supported TEER data and showed a stratified, non-keratinized multilayer of the optimized TR146 model. High-Throughput qPCR using 96 selected markers for keratinization, cornification, epithelial-mesenchymal transition, aquaporins, mucins, tight junctions, receptors, and transporter proteins was applied to comprehensively characterize the systematic optimization of the cellular model and validate against human biopsy samples. Data revealed the expression of several genes in the oral mucosa epithelium for the first time and elucidated novel regulations dependent on culture conditions. Moreover, functional activity of ABC transporters ABCB1 and ABCC4 was shown indicating the applicability of the model for drug transport studies. In conclusion, a Transwell model of the oral mucosa epithelium was optimized being suitable for transport studies.

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Section: Discussionmentioning

confidence: 72%

Optimization of an oral mucosa in vitro model based on cell line TR146

et al. 2020

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“…AQP1, 3, and 5 are expressed in different cells of the salivary gland. AQP5 has a major role in saliva secretion because Aqp5 KO mice had 60% reduced saliva secretion and produced more viscous saliva (Delporte et al, 2016). Patients with NGLY1-CDDG suffer from chronic constipation.…”

Section: Discussionmentioning

confidence: 99%

N-Glycanase 1 Transcriptionally Regulates Aquaporins Independent of Its Enzymatic Activity

Tambe

Freeze

2019

Cell Reports

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“…Besides being widely distributed among the human body, AQP5 was found expressed in salivary and lacrimal glands and showed to play a major role in saliva secretion [6]. AQP5 transport defect was also associated with Sjögren’s syndrome, a chronic autoimmune disease that destroys the salivary and lacrimal glands [6].…”

Section: Introductionmentioning

confidence: 99%

“…AQP5 transport defect was also associated with Sjögren’s syndrome, a chronic autoimmune disease that destroys the salivary and lacrimal glands [6]. More recently, AQP5 gained attention due its potential implication in carcinogenesis in different organs and systems [7].…”

Section: Introductionmentioning

confidence: 99%

Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

Rodrigues

Mósca

Martins

et al. 2016

IJMS

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Aquaporin-5 (AQP5) is a membrane water channel widely distributed in human tissues that was found up-regulated in different tumors and considered implicated in carcinogenesis in different organs and systems. Despite its wide distribution pattern and physiological importance, AQP5 short-term regulation was not reported and mechanisms underlying its involvement in cancer are not well defined. In this work, we expressed rat AQP5 in yeast and investigated mechanisms of gating, as well as AQP5’s ability to facilitate H2O2 plasma membrane diffusion. We found that AQP5 can be gated by extracellular pH in a phosphorylation-dependent manner, with higher activity at physiological pH 7.4. Moreover, similar to other mammalian AQPs, AQP5 is able to increase extracellular H2O2 influx and to affect oxidative cell response with dual effects: whereas in acute oxidative stress conditions AQP5 induces an initial higher sensitivity, in chronic stress AQP5 expressing cells show improved cell survival and resistance. Our findings support the involvement of AQP5 in oxidative stress and suggest AQP5 modulation by phosphorylation as a novel tool for therapeutics.

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Aquaporins in Salivary Glands: From Basic Research to Clinical Applications

Cited by 70 publications

References 120 publications

Optimization of an oral mucosa in vitro model based on cell line TR146

Optimization of an oral mucosa in vitro model based on cell line TR146

N-Glycanase 1 Transcriptionally Regulates Aquaporins Independent of Its Enzymatic Activity

Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

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