Aquaporin-1: New Developments and Perspectives for Peritoneal Dialysis

2010 ◽  
Vol 30 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Olivier Devuyst ◽  
Andrea J. Yool
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Water Channel ◽  
Cell Types ◽  
Convective Transport ◽  
Osmotic Gradient ◽  
Pharmacological Agents ◽  
Solute Permeability ◽  
Chemical Screening ◽  
Aquaporin 1

Peritoneal dialysis involves diffusive and convective transport and osmosis through the highly vascularized peritoneal membrane. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore predicted by the model of peritoneal transport. Proof-of-principle studies have shown that upregulation of the expression of AQP1 in peritoneal capillaries results in increased water permeability and ultrafiltration, without affecting the osmotic gradient or small solute permeability. Conversely, studies in Aqp1 mice have shown that haplo-insufficiency for AQP1 results in significant attenuation of water transport. Recent studies have demonstrated that AQP1 is involved in the migration of different cell types, including endothelial cells. In parallel, chemical screening has identified lead compounds that could act as antagonists or agonists of AQPs, with description of putative binding sites and potential mechanisms of gating the water channel. By modulating water transport, these pharmacological agents could have clinically relevant effects in targeting specific tissues or disease states.

In vivo inhibition of transcellular water channels (aquaporin-1) during acute peritoneal dialysis in rats

1996 ◽  
Vol 271 (6) ◽  
pp. H2254-H2262 ◽  
Author(s):  
O. Carlsson ◽  
S. Nielsen ◽  
el-R. Zakaria ◽  
B. Rippe
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Water Flow ◽  
Peritoneal Cavity ◽  
Critical Role ◽  
Water Channels ◽  
Capillary Endothelium ◽  
Tissue Fixation ◽  
Solute Permeability ◽  
Aquaporin 1

During peritoneal dialysis (PD), a major portion of the osmotically induced water transport to the peritoneum can be predicted to occur through endothelial water-selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the molecular correlate to such channels. Aquaporins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tissue fixation, used to protect the tissues from HgCl2 damage. Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1 labeling in capillary endothelium in peritoneal tissues, representing sites for HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and inhibited the sieving of Na+ without causing any untoward changes in microvascular permeability, compared with that of fixed control rats, in which the peritoneal cavity was exposed to tissue fixation alone. In fixed control rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats the dialysate Na+ concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibition of water flow through aquaporins. The observed HgCl2 inhibition of transcellular water channels strongly indicates a critical role of aquaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis.

scholarly journals Aquaporin-1 Facilitates Transmesothelial Water Permeability: In Vitro and Ex Vivo Evidence and Possible Implications in Peritoneal Dialysis

2021 ◽  
Vol 22 (22) ◽  
pp. 12535
Author(s):  
Francesca Piccapane ◽  
Andrea Gerbino ◽  
Monica Carmosino ◽  
Serena Milano ◽  
Arduino Arduini ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Peritoneal Dialysis ◽  
Tight Junctions ◽  
Water Transport ◽  
Water Flux ◽  
Water Channel ◽  
Bathing Solution ◽  
Ussing Chambers ◽  
Aquaporin 1 ◽  
Osmotic Water

We previously showed that mesothelial cells in human peritoneum express the water channel aquaporin 1 (AQP1) at the plasma membrane, suggesting that, although in a non-physiological context, it may facilitate osmotic water exchange during peritoneal dialysis (PD). According to the three-pore model that predicts the transport of water during PD, the endothelium of peritoneal capillaries is the major limiting barrier to water transport across peritoneum, assuming the functional role of the mesothelium, as a semipermeable barrier, to be negligible. We hypothesized that an intact mesothelial layer is poorly permeable to water unless AQP1 is expressed at the plasma membrane. To demonstrate that, we characterized an immortalized cell line of human mesothelium (HMC) and measured the osmotically-driven transmesothelial water flux in the absence or in the presence of AQP1. The presence of tight junctions between HMC was investigated by immunofluorescence. Bioelectrical parameters of HMC monolayers were studied by Ussing Chambers and transepithelial water transport was investigated by an electrophysiological approach based on measurements of TEA+ dilution in the apical bathing solution, through TEA+-sensitive microelectrodes. HMCs express Zo-1 and occludin at the tight junctions and a transepithelial vectorial Na+ transport. Real-time transmesothelial water flux, in response to an increase of osmolarity in the apical solution, indicated that, in the presence of AQP1, the rate of TEA+ dilution was up to four-fold higher than in its absence. Of note, we confirmed our data in isolated mouse mesentery patches, where we measured an AQP1-dependent transmesothelial osmotic water transport. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD through functional expression of the water channel AQP1.

Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice

1999 ◽  
Vol 276 (1) ◽  
pp. C76-C81 ◽  
Author(s):  
Baoxue Yang ◽  
Hans G. Folkesson ◽  
Jian Yang ◽  
Michael A. Matthay ◽  
Tonghui Ma ◽  
...  
Keyword(s):  
Water Transport ◽  
Peritoneal Cavity ◽  
Knockout Mice ◽  
Fluid Transport ◽  
Water Movement ◽  
Osmotic Gradient ◽  
Half Time ◽  
Aquaporin 1 ◽  
Osmotic Water ◽  
Major Route

Aquaporin-1 (AQP1) water channels are expressed widely in epithelia and capillary endothelia involved in fluid transport. To test whether AQP1 facilitates water movement from capillaries into the peritoneal cavity, osmotically induced water transport rates were compared in AQP1 knockout [(−/−)], heterozygous [(+/−)], and wild-type [(+/+)] mice. In (+/+) mice, RT-PCR showed detectable transcripts for AQP1, AQP3, AQP4, AQP7, and AQP8. Immunofluorescence showed AQP1 protein in capillary endothelia and mesangium near the peritoneal surface and AQP4 in adherent muscle plasmalemma. For measurement of water transport, 2 ml of saline containing 300 mM sucrose (600 mosM) were infused rapidly into the peritoneal cavity via a catheter. Serial fluid samples (50 μl) were withdrawn over 60 min, with albumin as a volume marker. The albumin dilution data showed significantly decreased initial volume influx in AQP1 (−/−) mice: 101 ± 8, 107 ± 5, and 42 ± 4 (SE) μl/min in (+/+), (+/−), and (−/−) mice, respectively [ n = 6–10, P < 0.001, (−/−) vs. others]. Volume influx for AQP4 knockout mice was 100 ± 8 μl/min. In the absence of an osmotic gradient,3H2O uptake [half time = 2.3 and 2.2 min in (+/+) and (−/−) mice, respectively], [14C]urea uptake [half time = 7.9 and 7.7 min in (+/+) and (−/−) mice, respectively], and spontaneous isosmolar fluid absorption from the peritoneal cavity [0.47 ± 0.05 and 0.46 ± 0.04 ml/h in (+/+) and (−/−) mice, respectively] were not affected by AQP1 deletion. Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis.

scholarly journals Immunoexpression of Aquaporin-1 in the Efferent Ducts of the Rat and Marmoset Monkey during Development, Its Modulation by Estrogens, and Its Possible Role in Fluid Resorption*

Endocrinology ◽  
1998 ◽  
Vol 139 (9) ◽  
pp. 3935-3945 ◽  
Author(s):  
Jane S. Fisher ◽  
Katie J. Turner ◽  
Hamish M. Fraser ◽  
Philippa T. K. Saunders ◽  
Dennis Brown ◽  
...  
Keyword(s):  
Hormonal Regulation ◽  
Water Channel ◽  
Cell Types ◽  
Rete Testis ◽  
Male Rats ◽  
Fetal Life ◽  
Neonatal Development ◽  
Gonadotropin Secretion ◽  
Aquaporin 1 ◽  
Efferent Ducts

Abstract Recent data suggest that estrogens play a role in regulating fluid resorption from the efferent ducts, though the biochemical mechanisms involved are unknown. The present study has used immunocytochemistry to localize a water channel protein, Aquaporin-1 (AQP-1), to the efferent ducts of male rats and marmoset monkeys from perinatal life through to adulthood and has then investigated its potential hormonal regulation in neonatal/peripubertal life, via administration of a GnRH antagonist (GnRHa) or diethylstilbestrol (DES) to rats. AQP-1 was immunoexpressed intensely in the apical brush border of the epithelium lining the efferent ducts at all ages studied, from late fetal life through puberty to adulthood. In the marmoset, but not the rat, AQP-1 was also expressed in the epithelium of the rete testis. Once the cell types within the efferent duct epithelium had differentiated, it was clear that only nonciliated cells of the rat localized AQP-1. When gonadotropin secretion was suppressed in rats by neonatal administration of GnRHa, immunoexpression of AQP-1 at age 18 and 25 days was virtually unchanged in intensity, though the efferent ducts were reduced in size. In contrast, when DES was administered neonatally to rats (up to day 12), immunoexpression of AQP-1 was reduced at day 10, virtually abolished at day 18, reduced markedly at day 25 and to a small extent at day 35; these findings were confirmed by Western blot analysis at day 18. The DES-induced decrease in immunoexpression of AQP-1 was accompanied by pronounced distension of the efferent ducts and rete, consistent with reduced fluid resorption. The epithelial cells of the efferent ducts in DES-treated rats were cuboidal rather than columnar in shape as in controls and were reduced significantly in height compared with controls at all ages through to adulthood. These findings suggest that estrogens may play a role in regulating fluid resorption from the efferent ducts during fetal/neonatal development and/or a role in the gross and functional development of the efferent ducts and rete testis. The present data also suggest that AQP-1 is one of the elements involved in the regulation of fluid resorption in the efferent ducts. The importance of fluid flow in fetal/neonatal development of the excurrent duct system of the male is also suggested by these observations.

scholarly journals P1130A CELLULAR MODEL OF HUMAN MESOTHELIUM TO STUDY OF WATER TRANSPORT DURING PERITONEAL DIALYSIS AND THE BIOCOMPATIBILITY OF INNOVATIVE GLUCOSE-SPARING SOLUTIONS.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Francesca Piccapane ◽  
Rosa Caroppo ◽  
Arduino Arduini ◽  
Roberto Corciulo ◽  
Roberto Russo ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Inflammatory Cytokines ◽  
Glucose Concentration ◽  
Water Channel ◽  
Mesothelial Cells ◽  
Dependent Manner ◽  
Endogenous Expression ◽  
Apical Side ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims The three pore model postulates that the endothelium of peritoneal capillaries is the major limiting barrier regulating water transport across peritoneal membrane during peritoneal dialysis (PD). We hypothesize that the mesothelium may represent an additional selective barrier to water diffusion in PD. We previously demonstrated that the water channel AQP1 is expressed in vivo by mesothelial cells. Here, we characterized an immortalized cell line of human mesothelium (HMC) to study the functional role of the water channel AQP1 in mediating water transport during PD and also to test the biocompatibility of glucose-sparing PD solutions (Xylocore), containing xylitol and L-carnitine as the main osmotic agents. Method Cells were grown onto porous cell culture inserts to achieve polarization. Polarization was demonstrated by expression of the tight junction markers Zo-1 and occludin. Transepithelial water transport was measured by TEA+-sensitive microelectrodes. HMC cell monolayers were exposed to PD solutions at the apical side for 8 hours. The biocompatibility of conventional versus innovative PD solutions was evaluated by MTT-test, measurement of transepithelial electrical resistance (TEER) and production of pro-inflammatory cytokines by by Luminex xMAP technology. Results HMC cells showed polarized expression of Na+/K+-ATPase and tight junctions markers but no endogenous expression of AQP1. HMC showed a low TEER (40Ω/cm2) compared to renal cells not expressing AQP1(1000Ω/cm2). However, the transepithelial water transport was comparable between the two cell types. Experiments in HMCs transfected with AQP1 cDNA, suggested that the water permeability of HMC was increased by two-fold in the presence of AQP1. Biocompatibility assays indicated that in conventional dialysis solutions glucose concentration decreased cell viability in a dose-dependent manner. Glucose concentration also strongly decreased the TEER, suggesting reduction of the barrier integrity, and increased pro-inflammatory cytokines production. Interestingly, substitution of part of the glucose with xylitol and L-carnitine minimized these effects. Conclusion These results suggest that the mesothelium may represent an additional selective barrier regulating water transport through the water channel AQP1 in PD. Importantly, we also demonstrate that the formulation of glucose-sparing PD solutions containing xylitol and L-carnitine better preserve mesothelial cells viability and may represent a useful means to prolong the dialysis life of patients undergoing peritoneal dialysis.

Expression of aquaporin-1 in a long-term peritoneal dialysis patient with impaired transcellular water transport

1999 ◽  
Vol 33 (2) ◽  
pp. 383-388 ◽  
Author(s):  
Eric Goffin ◽  
Sophie Combet ◽  
François Jamar ◽  
Jean-Pierre Cosyns ◽  
Olivier Devuyst
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Dialysis Patient ◽  
Peritoneal Dialysis Patient ◽  
Aquaporin 1

scholarly journals Can Free Water Transport be Used as a Clinical Parameter for Peritoneal Fibrosis in Long-Term PD Patients?

2016 ◽  
Vol 36 (2) ◽  
pp. 124-128 ◽  
Author(s):  
Raymond T. Krediet ◽  
Deirisa Lopes Barreto ◽  
Dirk G. Struijk
Keyword(s):  
Water Transport ◽  
Binding Capacity ◽  
Water Channel ◽  
Free Water ◽  
Clinical Parameter ◽  
Peritoneal Fibrosis ◽  
Water Binding ◽  
Aquaporin 1 ◽  
Normal Expression

Sodium sieving in peritoneal dialysis (PD) occurs in a situation with high osmotically-driven ultrafiltration rates. This dilutional phenomenon is caused by free water transport through the water channel aquaporin-1. It has recently been described that encapsulating peritoneal fibrosis is associated with impaired free water transport, despite normal expression of aquaporin-1. In this review, it will be argued that free water transport can be used for assessment of fibrotic peritoneal alterations, due to the water-binding capacity of collagen. Finally, the consequences for clinical practice will be discussed.

Quantification of osmotic water transport in vivo using fluorescent albumin

2014 ◽  
Vol 307 (8) ◽  
pp. F981-F989 ◽  
Author(s):  
Johann Morelle ◽  
Amadou Sow ◽  
Didier Vertommen ◽  
François Jamar ◽  
Bengt Rippe ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Transgenic Animals ◽  
Peritoneal Membrane ◽  
Intraperitoneal Pressure ◽  
Alexa Fluor ◽  
Osmotic Water

Osmotic water transport across the peritoneal membrane is applied during peritoneal dialysis to remove the excess water accumulated in patients with end-stage renal disease. The discovery of aquaporin water channels and the generation of transgenic animals have stressed the need for novel and accurate methods to unravel molecular mechanisms of water permeability in vivo. Here, we describe the use of fluorescently labeled albumin as a reliable indicator of osmotic water transport across the peritoneal membrane in a well-established mouse model of peritoneal dialysis. After detailed evaluation of intraperitoneal tracer mass kinetics, the technique was validated against direct volumetry, considered as the gold standard. The pH-insensitive dye Alexa Fluor 555-albumin was applied to quantify osmotic water transport across the mouse peritoneal membrane resulting from modulating dialysate osmolality and genetic silencing of the water channel aquaporin-1 (AQP1). Quantification of osmotic water transport using Alexa Fluor 555-albumin closely correlated with direct volumetry and with estimations based on radioiodinated (125I) serum albumin (RISA). The low intraperitoneal pressure probably accounts for the negligible disappearance of the tracer from the peritoneal cavity in this model. Taken together, these data demonstrate the appropriateness of pH-insensitive Alexa Fluor 555-albumin as a practical and reliable intraperitoneal volume tracer to quantify osmotic water transport in vivo.

scholarly journals Water transport and homeostasis as a major function of erythrocytes

2018 ◽  
Vol 314 (5) ◽  
pp. H1098-H1107 ◽  
Author(s):  
Joseph Sugie ◽  
Marcos Intaglietta ◽  
Lanping Amy Sung
Keyword(s):  
Water Transport ◽  
Volume Change ◽  
Interstitial Fluid ◽  
Water Exchange ◽  
Capillary Flow ◽  
The Body ◽  
Osmotic Gradient ◽  
Water Homeostasis ◽  
Major Function ◽  
Aquaporin 1

Erythrocytes have long been known to change volumes and shapes in response to different salt concentrations. Aquaporin-1 (AQP1) was discovered in their membranes more than 20 yr ago. The physiological roles of volume changes and AQP1 expression, however, have remained unclear. We propose that rapid water exchange through AQP1 coupled with large capacity for volume change may allow erythrocytes to play an important role in water regulation. In this study, we showed that erythrocytes in situ gradually reduced their volumes by 39% in response to the hyperosmotic corticomedullary gradient within mouse kidneys. AQP1 knockout (KO) erythrocytes, however, displayed only minimal reduction. Constructing a microfluidic device resembling capillary flow with an extracellular fluorescent reporter demonstrated that water exchanges between erythrocytes and their hypotonic or hypertonic surroundings in vitro reached steady state in ~60 ms. AQP1 KO erythrocytes, however, did not show significant change. To simulate the water transport in circulation, we built basic units consisting of three compartments (i.e., erythrocyte, plasma, and interstitial fluid) using Kedem-Katchalsky equations for membrane transport, and connected multiple units to account for the blood flow. These simulations agreed with experimental results. Importantly, volume-changing erythrocytes in capillaries always “increase” the osmotic gradient between plasma and interstitial fluid, making them function as “micropumps” to speed up the regulation of local osmolarity. Trillions of these micropumps, mobile throughout the body, may further contribute to water homeostasis. These insights suggest that the enhanced exchange of water, in addition to O2 and CO2, may well be the third major function of erythrocytes. NEW & NOTEWORTHY Physiological roles of erythrocyte volume change and aquaporin-1 were proposed and investigated here. We conclude that fast water transport by aquaporin-1 coupled with large volume-change capacity allows erythrocytes to enhance water exchange with local tissues. Furthermore, their huge number and mobility allow them to contribute to body water homeostasis.

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