Fundamentals of Bicarbonate Secretion in Epithelia

Novak, Ivana; Prætorius, Jeppe

doi:10.1007/978-1-4939-3366-2_5

Cited by 9 publications

(9 citation statements)

References 520 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the final saliva that enters the oral cavity is hypotonic and has low sodium concentration in comparison to plasma. Figure details the cellular mechanisms underlying formation of primary saliva …”

Section: Formation Of Primary Saliva and Ductal Salt Reabsorptionmentioning

confidence: 99%

Salivary secretion in health and disease

Pedersen

Sørensen

Proctor

et al. 2018

J of Oral Rehabilitation

344

269

View full text Add to dashboard Cite

Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction.

show abstract

Section: Formation Of Primary Saliva and Ductal Salt Reabsorptionmentioning

confidence: 99%

Salivary secretion in health and disease

Pedersen

Sørensen

Proctor

et al. 2018

J of Oral Rehabilitation

344

269

View full text Add to dashboard Cite

show abstract

“…The lower mRNA level of the cotransporter SLC4A4 in PDAC suggests that the pancreatic bicarbonate secretion and intracellular pH were dysregulated during PDAC development. SLC4A4 is an important protein in healthy pancreatic ducts, as the acid-base homeostasis is a key mechanism to control bicarbonate-rich fluid secretion [11]. As a bicarbonate transporter, SLC4A4 drives the transport of sodium and bicarbonate ions across the basolateral membrane of the pancreatic duct.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly in exocrine glands, the polarity of the epithelial cells is also essential for the control of the cellular absorption and secretion [8,10]. The pancreatic ductal system secretes an enormously bicarbonate-rich fluid, which is required to neutralize the acidic chime entering the duodenum and to provide an optimal pH microenvironment for the activity of digestive enzymes [11]. From a physiological perspective, the ion/fluid transport causes a transepithelial osmotic gradient that directly influences the intracellular volume [12,13].…”

Section: Introductionmentioning

confidence: 99%

The A818–6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer

et al. 2020

View full text Add to dashboard Cite

Background: The human pancreatic cancer cell line A818-6 can be grown in vitro either as a highly malignant, undifferentiated monolayer (ML) or as three-dimensional (3D) single layer hollow spheres (HS) simulating a benign, highly differentiated, duct-like pancreatic epithelial structure. This characteristic allowing A818-6 cells to switch from one phenotype to another makes these cells a unique system to characterize the cellular and molecular modifications during differentiation on one hand and malignant transformation on the other hand. Ion channels and transport proteins (transportome) have been implicated in malignant transformation. Therefore, the current study aimed to analyse the transportome gene expression profile in the A818-6 cells growing as a monolayer or as hollow spheres. Methods & Results: The study identified the differentially expressed transportome genes in both cellular states of A818-6 using Agilent and Nanostring arrays and some targets were validated via immunoblotting. Additionally, these results were compared to a tissue Affymetrix microarray analysis of pancreatic adenocarcinoma patients' tissues. The overall transcriptional profile of the ML and HS cells confirmed the formerly described mesenchymal features of ML and epithelial nature of HS which was further verified via high expression of E-cadherin and low expression of vimentin found in HS in comparison to ML. Among the predicted features between HS and ML was the involvement of miRNA-9 in this switch. Importantly, the bioinformatics analysis also revealed substantial number (n = 126) of altered transportome genes. Interestingly, three genes upregulated in PDAC tissue samples (GJB2, GJB5 and SLC38A6) were found to be also upregulated in ML and 3 down-regulated transportome genes (KCNQ1, TRPV6 and SLC4A) were also reduced in ML. Conclusion: This reversible HS/ML in vitro system might help in understanding the pathophysiological impact of the transportome in the dedifferentiation process in pancreatic carcinogenesis. Furthermore, the HS/ML model represents a novel system for studying the role of the transportome during the switch from a more benign, differentiated (HS) to a highly malignant, undifferentiated (ML) phenotype.

show abstract

Section: Introductionmentioning

confidence: 99%

“…In health, pancreatic duct epithelial cells secrete highly alkaline, bicarbonate-rich fluid, which is accomplished via luminal bicarbonate transport, balanced by basolateral export of protons into the interstitial extracellular environment [11,12]. To achieve this function, while maintaining intracellular pH homeostasis, pancreatic duct cells are equipped with specific, tightly regulated, acid/base transporters [12]. This special feature leaves pancreatic duct cells well-adapted to survival in a milieu characterized by pH fluctuations, which, under pathological conditions such as cancer, also leaves them pre-adapted to the selection pressure present in the acidified extracellular environment of PDAC [13].…”

Section: Introductionmentioning

confidence: 99%

Proton Pump Inhibitors Reduce Pancreatic Adenocarcinoma Progression by Selectively Targeting H+, K+-ATPases in Pancreatic Cancer and Stellate Cells

Tozzi

Sørensen

Magni

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Pancreatic duct cells are equipped with acid/base transporters important for exocrine secretion. Pancreatic ductal adenocarcinoma (PDAC) cells may utilize such transporters to acidify extracellular tumor microenvironment, creating a niche favoring cell proliferation, fibrosis and resistance to chemotherapy—all contributing to the notoriously bad prognosis of this disease. Here, we report that gastric and non-gastric H+, K+-ATPases (coded by ATP4A and ATP12A) are overexpressed in human and murine pancreatic cancer and that we can target them specifically with proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) in in vitro models of PDAC. Focusing on pantoprazole, we show that it significantly reduced human cancer cell proliferation by inhibiting cellular H+ extrusion, increasing K+ conductance and promoting cyclin D1-dependent cell cycle arrest and preventing STAT3 activation. Pantoprazole also decreased collagen secretion from pancreatic stellate cells. Importantly, in vivo studies show that pantoprazole treatment of tumor-bearing mice reduced tumor size, fibrosis and expression of angiogenic markers. This work provides the first evidence that H+, K+-ATPases contribute to PDAC progression and that these can be targeted by inhibitors of these pumps, thus proving a promising therapeutic strategy.

show abstract

Fundamentals of Bicarbonate Secretion in Epithelia

Cited by 9 publications

References 520 publications

Salivary secretion in health and disease

Salivary secretion in health and disease

The A818–6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer

Proton Pump Inhibitors Reduce Pancreatic Adenocarcinoma Progression by Selectively Targeting H+, K+-ATPases in Pancreatic Cancer and Stellate Cells

Contact Info

Product

Resources

About