The Human Aquaporin-5 Gene

Lee, M. Douglas; Bhakta, Kushal Y.; Raina, Surabhi; Yonescu, Raluca; Griffin, Constance A.; Copeland, Neal G.; Gilbert, Debra J.; Jenkins, Nancy A.; Preston, Gregory M.; Agre, Peter

doi:10.1074/jbc.271.15.8599

Cited by 90 publications

(36 citation statements)

References 43 publications

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“…Of relevance to this report is a mouse quantitative trait locus (QTL) genetic mapping study performed by De Sanctis and colleagues (9). Airway hyperresponsiveness was mapped to mouse chromosome 15 (9) in the same region as the Aqp5 gene locus (12). Two studies have mapped major asthma-susceptibility loci on human chromosome 12q (10,11), the chromosomal location of human Aqp5 gene (12).…”

Section: Discussionmentioning

confidence: 99%

“…Airway hyperresponsiveness was mapped to mouse chromosome 15 (9) in the same region as the Aqp5 gene locus (12). Two studies have mapped major asthma-susceptibility loci on human chromosome 12q (10,11), the chromosomal location of human Aqp5 gene (12). Human chromosome 12q and mouse chromosome 15 are syntenic within this region, which contains an aquaporin gene cluster (12,13).…”

Section: Discussionmentioning

confidence: 99%

“…Two studies have mapped major asthma-susceptibility loci on human chromosome 12q (10,11), the chromosomal location of human Aqp5 gene (12). Human chromosome 12q and mouse chromosome 15 are syntenic within this region, which contains an aquaporin gene cluster (12,13). None of the above linkage reports identify Aqp5 as a candidate gene locus for asthma or bronchial hyperreactivity.…”

Section: Discussionmentioning

confidence: 99%

“…Our results show a novel role for AQP5 in airway responsiveness. Interestingly, previously reported genetic linkage studies identify syntenic regions of mouse chromosome 15 (9) and human chromosome 12q (10,11), in which Aqp5 resides (12,13), as containing loci linked with hyperreactivity to bronchoconstriction. This genetic evidence supports the physiological results presented here, which implicate AQP5 in the pathogenesis of bronchial hyperreactivity.…”

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confidence: 99%

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Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Krane

Fortner

Hand

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

106

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Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveolar type II cells, and in tracheal and bronchial epithelium. Aqp5 knockout (Aqp5 ؊/؊ ) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp5 ؉/؉ mice, Aqp5 ؊/؊ mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp5 ؊/؊ mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5 ؊/؊ mice was not due to differences in tracheal smooth muscle contractility in isolated preparations or to altered levels of surfactant protein B. These data suggest a novel pathway by which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene.A quaporin 5 (AQP5) is a mercury-sensitive water channel expressed in mouse salivary gland acinar cells, alveolar type I cells, lacrimal glands, and the eye (1-3). However, the function of AQP5 in mouse lung physiology and pathophysiology is largely unknown. Recent studies have explored the regulation of Aqp5 gene expression in normal and disease states. In a mouse model of acute lung injury, AQP5 mRNA and protein expression were significantly decreased in association with pulmonary inflammation and edema resulting from adenoviral infection (4). Moreover, AQP5 expression in a murine lung epithelial cell line (MLE-12) is modulated by the proinf lammatory cytokine TNF-␣ through an nuclear factor (NF)-B-dependent pathway (5). Keratinocyte growth factor also has been shown to mediate the differentiation status of alveolar epithelial cells and AQP5 expression (6). However, a clear understanding of AQP5 function in the lung remains to be discerned.Previously published studies have addressed functional questions limited to the examination of the role of AQP5 in type I cells in fluid clearance and airspace-capillary osmotic water permeability. Of significance, isolated perfused lungs from Aqp5 Ϫ/Ϫ mice were shown to have a 10-fold reduction in airspace-capillary osmotic water permeability (7). Experiments addressing the role of AQP5 in alveolar fluid clearance failed to indicate a role for AQP5 in this process under certain physiological conditions (8). Based on the results of these studies, some have concluded that AQP5 does not play a major role in lung physiology. Contrary to these conclusions, the data reported here clearly define a...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Krane

Fortner

Hand

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

106

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“…12 Treatment with a DNA demethylating agent, such as 5-aza-2 0 -deoxycytidine (5-Aza-CdR), reactivates many genes that have been inactivated by hypermethylation. [13][14][15][16][17] However, although the AQP5 promoter contains three consensus Sp1-binding sites, 18 the relationship between the methylation status of the AQP5 promoter and the gene expression has not yet been examined in human salivary gland cells.…”

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confidence: 99%

Expression of aquaporin-5 in and fluid secretion from immortalized human salivary gland ductal cells by treatment with 5-aza-2′-deoxycytidine: a possibility for improvement of xerostomia in patients with Sjögren's syndrome

Motegi

Azuma

Tamatani

et al. 2005

Laboratory Investigation

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The aim of the present study was to investigate the possibility that ductal cells, which preferentially survive and/ or proliferate in Sjö gren's syndrome (SS) salivary glands of patients with SS, could acquire the functional expression of membrane water channel aquaporin-5 (AQP5). Thus, in this study, we demonstrate that an immortalized normal human salivary gland ductal cell (NS-SV-DC) line, lacking the expression of AQP5, acquires AQP5 gene expression in response to treatment with 5-aza-2 0 -deoxycytidine (5-Aza-CdR), a DNA demethylating agent. Confocal microscopic analysis revealed the localization of AQP5 expression mainly at the apical and lateral sides of the plasma membrane. The expressed AQP5 protein was functionally active because AQP5 expression resulted in a significant increase in the osmotically directed net fluid rate across monolayers of NS-SV-DC cells. By the analysis of bisulfite sequencing of CpG islands in the AQP5 promoter, hypermethylation within the consensus Sp1-binding sites was commonly observed in parental cell clones, whereas demethylation at the CGs, one in the second consensus Sp1 element and the other outside of the third consensus Sp1 element in the AQP5 promoter, was detected in NS-SV-DC cells after treatment with 5-Aza-CdR. By analyzing the luciferase activity of transfected AQP5 promoter vectors, it became evident that demethylation at the CGs cooperatively functions between these two sites to induce AQP5 expression. Our data, therefore, suggest that treatment of ductal cells with 5-Aza-CdR could result in the expression of the AQP5 gene, thereby leading to increased fluid secretion from ductal cells in SS salivary glands.

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Epithelial Transport

Reuss

1997

Comprehensive Physiology

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The sections in this article are: Transporting Epithelia Are Sheets of Polar Cells Epithelial Structure Involves Specialized Cell–Cell and Cell–Matrix Junctions Epithelial Polarity Is Essential for Vectorial Transport Transporting Epithelia Generate and Maintain Differences in Chemical Composition Between Fluid Compartments Transepithelial Transport Involves Active Ion Transport Passive Transport Processes also Contribute to Transepithelial Transport Transepithelial Transport Involves Transcellular and Paracellular Pathways Chemical and Electrical Gradients Couple Ion Fluxes in Epithelia The Building Blocks of Epithelial Function Are Membrane Transporters Mechanisms of Ion Transport The Two‐Membrane Hypothesis: A General Epithelial‐Transport Model Mechanisms of Transepithelial NaCl Transport in Absorptive Epithelia Mechanisms of Ion Transport in Primary Cl − ‐Transporting Epithelia Mechanisms of Ion Transport in H + — and ‐Transporting Epithelia Mechanisms of Transepithelial Water Transport Transepithelial Water Transport Is Linked to Transepithelial Salt Transport Epithelia Are Widely Diverse in Their Water‐Transport Characteristics Transepithelial Water Transport in Leaky Epithelia Is Nearly Isosmotic Transepithelial Water Transport in Leaky Epithelia Can Be Transcellular and/or Paracellular Water Permeation across Cell Membranes of Some Leaky Epithelia Is via Constitutive Pores Mechanisms of Transepithelial Water Transport in ADH ‐Sensitive Epithelia Molecular Identity of Water Pores in Epithelial‐Cell Membranes Mechanisms of Regulation of Transepithelial Transport Rapid Regulation Long‐term Regulation Intramembrane Regulation and Cross‐Talk Mechanisms

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The Human Aquaporin-5 Gene

Abstract: The cDNA for the fifth mammalian aquaporin (AQP5) was isolated from rat, and expression was demonstrated in rat salivary and lacrimal glands, cornea, and lung (Raina, S., Preston, G. M., Guggino, W. B., and Agre, P.

Cited by 90 publications

References 43 publications

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Expression of aquaporin-5 in and fluid secretion from immortalized human salivary gland ductal cells by treatment with 5-aza-2′-deoxycytidine: a possibility for improvement of xerostomia in patients with Sjögren's syndrome

Epithelial Transport

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