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Open AccessEditorial

Advances in Aquaporins

by Giuseppe Calamita

Cells 2023, 12(2), 303; https://doi.org/10.3390/cells12020303 - 13 Jan 2023

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Abstract

[Aquaporins (AQPs) are a family of transmembrane channel proteins, widespread...] Full article

(This article belongs to the Special Issue Advances in Aquaporins)

Research

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17 pages, 7983 KiB

Open AccessArticle

Ablation of Aquaporin-9 Ameliorates the Systemic Inflammatory Response of LPS-Induced Endotoxic Shock in Mouse

by Angela Tesse, Patrizia Gena, Michael Rützler and Giuseppe Calamita

Cells 2021, 10(2), 435; https://doi.org/10.3390/cells10020435 - 18 Feb 2021

Cited by 21 | Viewed by 3472

Abstract

Septic shock is the most severe complication of sepsis, being characterized by a systemic inflammatory response following bacterial infection, leading to multiple organ failure and dramatically high mortality. Aquaporin-9 (AQP9), a membrane channel protein mainly expressed in hepatocytes and leukocytes, has been recently [...] Read more.

Septic shock is the most severe complication of sepsis, being characterized by a systemic inflammatory response following bacterial infection, leading to multiple organ failure and dramatically high mortality. Aquaporin-9 (AQP9), a membrane channel protein mainly expressed in hepatocytes and leukocytes, has been recently associated with inflammatory and infectious responses, thus triggering strong interest as a potential target for reducing septic shock-dependent mortality. Here, we evaluated whether AQP9 contributes to murine systemic inflammation during endotoxic shock. Wild type (Aqp9^+/+; WT) and Aqp9 gene knockout (Aqp9^−/−; KO) male mice were submitted to endotoxic shock by i.p. injection of lipopolysaccharide (LPS; 40 mg/kg) and the related survival times were followed during 72 h. The electronic paramagnetic resonance and confocal microscopy were employed to analyze the nitric oxide (NO) and superoxide anion (O₂⁻) production, and the expression of inducible NO-synthase (iNOS) and cyclooxigenase-2 (COX-2), respectively, in the liver, kidney, aorta, heart and lung of the mouse specimens. LPS-treated KO mice survived significantly longer than corresponding WT mice, and 25% of the KO mice fully recovered from the endotoxin treatment. The LPS-injected KO mice showed lower inflammatory NO and O₂⁻ productions and reduced iNOS and COX-2 levels through impaired NF-κB p65 activation in the liver, kidney, aorta, and heart as compared to the LPS-treated WT mice. Consistent with these results, the treatment of FaO cells, a rodent hepatoma cell line, with the AQP9 blocker HTS13268 prevented the LPS-induced increase of inflammatory NO and O₂⁻. A role for AQP9 is suggested in the early acute phase of LPS-induced endotoxic shock involving NF-κB signaling. The modulation of AQP9 expression/function may reveal to be useful in developing novel endotoxemia therapeutics. Full article

(This article belongs to the Special Issue Advances in Aquaporins)

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17 pages, 3362 KiB

Open AccessFeature PaperArticle

Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+

by Agnete Prydz, Katja Stahl, Soulmaz Zahl, Nadia Skauli, Øivind Skare, Ole Petter Ottersen and Mahmood Amiry-Moghaddam

Cells 2020, 9(11), 2418; https://doi.org/10.3390/cells9112418 - 5 Nov 2020

Cited by 14 | Viewed by 3702

Abstract

Aquaporin-4 (AQP4) is critically involved in brain water and volume homeostasis and has been implicated in a wide range of pathological conditions. Notably, evidence has been accrued to suggest that AQP4 plays a proinflammatory role by promoting release of astrocytic cytokines that activate [...] Read more.

Aquaporin-4 (AQP4) is critically involved in brain water and volume homeostasis and has been implicated in a wide range of pathological conditions. Notably, evidence has been accrued to suggest that AQP4 plays a proinflammatory role by promoting release of astrocytic cytokines that activate microglia and other astrocytes. Neuroinflammation is a hallmark of Parkinson’s disease (PD), and we have previously shown that astrocytes in substantia nigra (SN) are enriched in AQP4 relative to cortical astrocytes, and that their complement of AQP4 is further increased following treatment with the parkinsonogenic toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Here, we investigated the effect of Aqp4 deletion on microglial activation in mice subjected to unilateral intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP+, the toxic metabolite of MPTP). Our results show that MPP+ injections lead to a pronounced increase in the expression level of microglial activating genes in the ventral mesencephalon of wild type (WT) mice, but not Aqp4^−/− mice. We also show, in WT mice, that MPP+ injections cause an upregulation of nigral AQP4 and swelling of astrocytic endfeet. These findings are consistent with the idea that AQP4 plays a pro-inflammatory role in Parkinson’s disease, secondary to the dysregulation of astrocytic volume homeostasis. Full article

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12 pages, 2814 KiB

Open AccessArticle

The Ionophores CCCP and Gramicidin but Not Nigericin Inhibit Trypanosoma brucei Aquaglyceroporins at Neutral pH

by Lea Madlen Petersen and Eric Beitz

Cells 2020, 9(10), 2335; https://doi.org/10.3390/cells9102335 - 21 Oct 2020

Cited by 2 | Viewed by 3122

Abstract

Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei parasites. The T. brucei aquaglyceroporin isoform 2, TbAQP2, has been linked to the uptake of pentamidine. Negative membrane potentials and transmembrane pH gradients were suggested to promote transport of the dicationic antitrypanosomal drug. Application [...] Read more.

Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei parasites. The T. brucei aquaglyceroporin isoform 2, TbAQP2, has been linked to the uptake of pentamidine. Negative membrane potentials and transmembrane pH gradients were suggested to promote transport of the dicationic antitrypanosomal drug. Application of ionophores to trypanosomes further hinted at direct inhibition of TbAQP2 by carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Here, we tested for direct effects of three classical ionophores (CCCP, nigericin, gramicidin) on the functionality of TbAQP2 and the related TbAQP3 at conditions that are independent from the membrane potential or a proton gradient. We expressed TbAQP2 and TbAQP3 in yeast, and determined permeability of uncharged glycerol at neutral pH using stopped-flow light scattering. The mobile proton carrier CCCP directly inhibited TbAQP2 glycerol permeability at an IC₅₀ of 2 µM, and TbAQP3 to a much lesser extent (IC₅₀ around 1 mM) likely due to different selectivity filter layouts. Nigericin, another mobile carrier, left both isoforms unaffected. The membrane-integral pore-forming gramicidin evenly inhibited TbAQP2 and TbAQP2 in the double-digit micromolar range. Our data exemplify the need for suitable controls to detect unwanted ionophore side effects even when used at concentrations that are typically recommended to disturb the transmembrane ion distribution. Full article

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20 pages, 4165 KiB

Open AccessArticle

Blockade of 67-kDa Laminin Receptor Facilitates AQP4 Down-Regulation and BBB Disruption via ERK1/2-and p38 MAPK-Mediated PI3K/AKT Activations

by Ji-Eun Kim, Hana Park, Ji-Eun Lee and Tae-Cheon Kang

Cells 2020, 9(7), 1670; https://doi.org/10.3390/cells9071670 - 11 Jul 2020

Cited by 14 | Viewed by 4105

Abstract

Recently, we have reported that dysfunctions of 67-kDa laminin receptor (67LR) induced by status epilepticus (SE, a prolonged seizure activity) and 67LR neutralization are involved in vasogenic edema formation, accompanied by the reduced aquaporin 4 (AQP4, an astroglial specific water channel) expression in [...] Read more.

Recently, we have reported that dysfunctions of 67-kDa laminin receptor (67LR) induced by status epilepticus (SE, a prolonged seizure activity) and 67LR neutralization are involved in vasogenic edema formation, accompanied by the reduced aquaporin 4 (AQP4, an astroglial specific water channel) expression in the rat piriform cortex (PC). In the present study, we found that the blockade of 67LR activated p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways, which enhanced phosphatidylinositol 3 kinase (PI3K)/AKT phosphorylations in endothelial cells and astrocytes, respectively. 67LR-p38 MAPK-PI3K-AKT activation in endothelial cells increased vascular permeability. In contrast, 67LR-ERK1/2-PI3K-AKT signaling pathways in astrocytes regulated astroglial viability and AQP4 expression. These findings indicate that PI3K/AKT may integrate p38 MAPK and ERK1/2 signaling pathways to regulate AQP4 expression when 67LR functionality is reduced. Thus, we suggest that 67LR-p38 MAPK/ERK1/2-PI3K-AKT-AQP4 signaling cascades may mediate serum extravasation and AQP4 expression in astroglio-vascular systems, which is one of the considerable therapeutic targets for vasogenic edema in various neurological diseases. Full article

(This article belongs to the Special Issue Advances in Aquaporins)

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29 pages, 8423 KiB

Open AccessFeature PaperArticle

Unravelling the Complex Duplication History of Deuterostome Glycerol Transporters

by Ozlem Yilmaz, François Chauvigné, Alba Ferré, Frank Nilsen, Per Gunnar Fjelldal, Joan Cerdà and Roderick Nigel Finn

Cells 2020, 9(7), 1663; https://doi.org/10.3390/cells9071663 - 10 Jul 2020

Cited by 16 | Viewed by 3408

Abstract

Transmembrane glycerol transport is an ancient biophysical property that evolved in selected subfamilies of water channel (aquaporin) proteins. Here, we conducted broad level genome (>550) and transcriptome (>300) analyses to unravel the duplication history of the glycerol-transporting channels (glps) in Deuterostomia. [...] Read more.

Transmembrane glycerol transport is an ancient biophysical property that evolved in selected subfamilies of water channel (aquaporin) proteins. Here, we conducted broad level genome (>550) and transcriptome (>300) analyses to unravel the duplication history of the glycerol-transporting channels (glps) in Deuterostomia. We found that tandem duplication (TD) was the major mechanism of gene expansion in echinoderms and hemichordates, which, together with whole genome duplications (WGD) in the chordate lineage, continued to shape the genomic repertoires in craniates. Molecular phylogenies indicated that aqp3-like and aqp13-like channels were the probable stem subfamilies in craniates, with WGD generating aqp9 and aqp10 in gnathostomes but aqp7 arising through TD in Osteichthyes. We uncovered separate examples of gene translocations, gene conversion, and concerted evolution in humans, teleosts, and starfishes, with DNA transposons the likely drivers of gene rearrangements in paleotetraploid salmonids. Currently, gene copy numbers and BLAST are poor predictors of orthologous relationships due to asymmetric glp gene evolution in the different lineages. Such asymmetries can impact estimations of divergence times by millions of years. Experimental investigations of the salmonid channels demonstrated that approximately half of the 20 ancestral paralogs are functional, with neofunctionalization occurring at the transcriptional level rather than the protein transport properties. The combined findings resolve the origins and diversification of glps over >800 million years old and thus form the novel basis for proposing a pandeuterostome glp gene nomenclature. Full article

(This article belongs to the Special Issue Advances in Aquaporins)

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19 pages, 1272 KiB

Open AccessArticle

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

by Katharina Rump, Tim Rahmel, Anna-Maria Rustige, Matthias Unterberg, Hartmuth Nowak, Björn Koos, Peter Schenker, Richard Viebahn, Michael Adamzik and Lars Bergmann

Cells 2020, 9(6), 1421; https://doi.org/10.3390/cells9061421 - 8 Jun 2020

Cited by 7 | Viewed by 2507

Abstract

Major complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and we explored the [...] Read more.

Major complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and we explored the effect of AQP3 polymorphism on immune cell function and its association with graft rejection and CMV infection in 237 adult patients within 12 months after transplantation. AQP3 promoter polymorphism was molecular and functional characterized. Kaplan–Meier plots evaluated the relationship between genotypes and the incidence of CMV infection and graft rejection. AQP3 A(−1431)G A-allele was associated with enhanced immune cell migration and AQP3 expression in T-cells. The incidences of rejection were 45.4% for the A-allele and 27.1% for G-allele carriers (p = 0.005) and the A-allele was a strong risk factor (hazard ratio (HR): 1.95; 95% CI: 1.216 to 3.127; p = 0.006). The incidences for CMV infection were 21% for A-allele and 35% for G-allele carriers (p = 0.013) and G-allele was an independent risk factor (p = 0.023), with a doubled risk for CMV infection (HR: 1.9; 95% CI: 1.154 to 3.128; p = 0.012). Hence, A-allele confers more resistance against CMV infection, but susceptibility to graft rejection mediated by T-cells. Thus, AQP3-genotype adapted management of immunosuppression and antiviral prophylaxis after kidney transplantation seems prudent. Full article

(This article belongs to the Special Issue Advances in Aquaporins)

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14 pages, 2240 KiB

Open AccessArticle

Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation

by Gema Frühbeck, Inmaculada Balaguer, Leire Méndez-Giménez, Víctor Valentí, Sara Becerril, Victoria Catalán, Javier Gómez-Ambrosi, Camilo Silva, Javier Salvador, Giuseppe Calamita, María M. Malagón and Amaia Rodríguez

Cells 2020, 9(6), 1403; https://doi.org/10.3390/cells9061403 - 4 Jun 2020

Cited by 31 | Viewed by 3754

Abstract

Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H₂O₂), we hypothesized that this superaquaporin is involved in ER stress [...] Read more.

Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H₂O₂), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-α, and particularly TGF-β1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-β1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-β1-induced ER stress in visceral adipocytes. Owing to its “peroxiporin” properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity. Full article

(This article belongs to the Special Issue Advances in Aquaporins)

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11 pages, 1143 KiB

Open AccessArticle

Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study

by Lars Bergmann, Hartmuth Nowak, Winfried Siffert, Jürgen Peters, Michael Adamzik, Björn Koos and Tim Rahmel

Cells 2020, 9(4), 904; https://doi.org/10.3390/cells9040904 - 7 Apr 2020

Cited by 6 | Viewed by 2640

Abstract

Since the functionally important AQP5 -1364A/C single nucleotide promoter polymorphism alters key mechanisms of inflammation and survival in sepsis, it may affect the risk of an acute kidney injury. Accordingly, we tested the hypothesis in septic patients that this AQP5 polymorphism is associated [...] Read more.

Since the functionally important AQP5 -1364A/C single nucleotide promoter polymorphism alters key mechanisms of inflammation and survival in sepsis, it may affect the risk of an acute kidney injury. Accordingly, we tested the hypothesis in septic patients that this AQP5 polymorphism is associated with major adverse kidney events and also validated its impact on 90-day survival. In this prospective observational monocentric genetic association study 282 septic patients were included and genotyped for the AQP5 –1364A/C polymorphism (rs3759129). The primary endpoint was the development of major adverse kidney events within 30 days. In AC/CC genotypes, major adverse kidney events were less frequent (41.7%) than in AA genotypes (74.3%; OR:0.34; 95%-CI: 0.18–0.62; p < 0.001). Ninety-day survival was also associated with the AQP5 polymorphism (p = 0.004), with 94/167 deaths (56.3%) in AA genotypes, but only 46/115 deaths (40.0%) in C-allele carriers. Multiple proportional hazard analysis revealed AC/CC genotypes to be at significantly lower risk for death within 90 days (HR: 0.60; 95%-CI: 0.42-0.86; p = 0.006). These findings confirm the important role of the AQP5 -1364A/C polymorphism as an independent prognostic factor in sepsis. Furthermore, we demonstrate a strong association between this AQP5 polymorphism and susceptibility for major adverse kidney events suggesting a promising characteristic in terms of precision medicine. Full article

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Review

Jump to: Editorial, Research

18 pages, 1939 KiB

Open AccessReview

Targeting Aquaporins in Novel Therapies for Male and Female Breast and Reproductive Cancers

by Sidra Khan, Carmela Ricciardelli and Andrea J. Yool

Cells 2021, 10(2), 215; https://doi.org/10.3390/cells10020215 - 22 Jan 2021

Cited by 16 | Viewed by 4578

Abstract

Aquaporins are membrane channels in the broad family of major intrinsic proteins (MIPs), with 13 classes showing tissue-specific distributions in humans. As key physiological modulators of water and solute homeostasis, mutations, and dysfunctions involving aquaporins have been associated with pathologies in all major [...] Read more.

Aquaporins are membrane channels in the broad family of major intrinsic proteins (MIPs), with 13 classes showing tissue-specific distributions in humans. As key physiological modulators of water and solute homeostasis, mutations, and dysfunctions involving aquaporins have been associated with pathologies in all major organs. Increases in aquaporin expression are associated with greater severity of many cancers, particularly in augmenting motility and invasiveness for example in colon cancers and glioblastoma. However, potential roles of altered aquaporin (AQP) function in reproductive cancers have been understudied to date. Published work reviewed here shows distinct classes aquaporin have differential roles in mediating cancer metastasis, angiogenesis, and resistance to apoptosis. Known mechanisms of action of AQPs in other tissues are proving relevant to understanding reproductive cancers. Emerging patterns show AQPs 1, 3, and 5 in particular are highly expressed in breast, endometrial, and ovarian cancers, consistent with their gene regulation by estrogen response elements, and AQPs 3 and 9 in particular are linked with prostate cancer. Continuing work is defining avenues for pharmacological targeting of aquaporins as potential therapies to reduce female and male reproductive cancer cell growth and invasiveness. Full article

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17 pages, 1227 KiB

Open AccessReview

Role of Aquaporins in the Physiological Functions of Mesenchymal Stem Cells

by Antonella Zannetti, Gheorghe Benga, Arturo Brunetti, Francesco Napolitano, Luigi Avallone and Alessandra Pelagalli

Cells 2020, 9(12), 2678; https://doi.org/10.3390/cells9122678 - 13 Dec 2020

Cited by 21 | Viewed by 3798

Abstract

Aquaporins (AQPs) are a family of membrane water channel proteins that control osmotically-driven water transport across cell membranes. Recent studies have focused on the assessment of fluid flux regulation in relation to the biological processes that maintain mesenchymal stem cell (MSC) physiology. In [...] Read more.

Aquaporins (AQPs) are a family of membrane water channel proteins that control osmotically-driven water transport across cell membranes. Recent studies have focused on the assessment of fluid flux regulation in relation to the biological processes that maintain mesenchymal stem cell (MSC) physiology. In particular, AQPs seem to regulate MSC proliferation through rapid regulation of the cell volume. Furthermore, several reports have shown that AQPs play a crucial role in modulating MSC attachment to the extracellular matrix, their spread, and migration. Shedding light on how AQPs are able to regulate MSC physiological functions can increase our knowledge of their biological behaviours and improve their application in regenerative and reparative medicine. Full article

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19 pages, 1082 KiB

Open AccessReview

Insights into Cell Surface Expression, Supramolecular Organization, and Functions of Aquaporin 4 Isoforms in Astrocytes

by Jernej Jorgačevski, Robert Zorec and Maja Potokar

Cells 2020, 9(12), 2622; https://doi.org/10.3390/cells9122622 - 7 Dec 2020

Cited by 28 | Viewed by 4631

Abstract

Aquaporin 4 (AQP4) is the most abundant water channel in the central nervous system (CNS). Its expression is confined to non-neuronal glial cells, predominantly to astrocytes that represent a heterogeneous glial cell type in the CNS. The membrane of astrocyte processes, which align [...] Read more.

Aquaporin 4 (AQP4) is the most abundant water channel in the central nervous system (CNS). Its expression is confined to non-neuronal glial cells, predominantly to astrocytes that represent a heterogeneous glial cell type in the CNS. The membrane of astrocyte processes, which align brain capillaries and pia, is particularly rich in AQP4. Several isoforms of AQP4 have been described; however, only some (AQP4a (M1), AQP4 c (M23), AQP4e, and AQP4ex) have been identified in the plasma membrane assemblies of astrocytes termed orthogonal arrays of particles (OAPs). Intracellular splicing isoforms (AQP4b, AQP4d, AQP4f, AQP4-Δ4) have been documented, and most of them are postulated to have a role in the cell surface distribution of the plasma membrane isoforms and in the formation of OAPs in murine and human astrocytes. Although OAPs have been proposed to play various roles in the functioning of astrocytes and CNS tissue as a whole, many of these still need to be described. OAPs are studied primarily from the perspective of understanding water permeability regulation through the plasma membrane and of their involvement in cell adhesion and in the dynamics of astrocytic processes. This review describes the cellular distribution of various AQP4 isoforms and their implications in OAP assembly, which is regulated by several intracellular and extracellular proteins. Full article

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25 pages, 2550 KiB

Open AccessReview

The Relevance of Aquaporins for the Physiology, Pathology, and Aging of the Female Reproductive System in Mammals

by Paweł Kordowitzki, Wiesława Kranc, Rut Bryl, Bartosz Kempisty, Agnieszka Skowronska and Mariusz T. Skowronski

Cells 2020, 9(12), 2570; https://doi.org/10.3390/cells9122570 - 1 Dec 2020

Cited by 14 | Viewed by 4426

Abstract

Aquaporins constitute a group of water channel proteins located in numerous cell types. These are pore-forming transmembrane proteins, which mediate the specific passage of water molecules through membranes. It is well-known that water homeostasis plays a crucial role in different reproductive processes, e.g., [...] Read more.

Aquaporins constitute a group of water channel proteins located in numerous cell types. These are pore-forming transmembrane proteins, which mediate the specific passage of water molecules through membranes. It is well-known that water homeostasis plays a crucial role in different reproductive processes, e.g., oocyte transport, hormonal secretion, completion of successful fertilization, blastocyst formation, pregnancy, and birth. Further, aquaporins are involved in the process of spermatogenesis, and they have been reported to be involved during the storage of spermatozoa. It is noteworthy that aquaporins are relevant for the physiological function of specific parts in the female reproductive system, which will be presented in detail in the first section of this review. Moreover, they are relevant in different pathologies in the female reproductive system. The contribution of aquaporins in selected reproductive disorders and aging will be summarized in the second section of this review, followed by a section dedicated to aquaporin-related proteins. Since the relevance of aquaporins for the male reproductive system has been reviewed several times in the recent past, this review aims to provide an update on the distribution and impact of aquaporins only in the female reproductive system. Therefore, this paper seeks to determine the physiological and patho-physiological relevance of aquaporins on female reproduction, and female reproductive aging. Full article

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18 pages, 837 KiB

Open AccessReview

AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions

by Chao Gao, Paul J. Higgins and Wenzheng Zhang

Cells 2020, 9(10), 2172; https://doi.org/10.3390/cells9102172 - 26 Sep 2020

Cited by 24 | Viewed by 4622

Abstract

As a rare hereditary disease, congenital nephrogenic diabetes insipidus (NDI) is clinically characterized by polyuria with hyposthenuria and polydipsia. NDI results from collecting duct principal cell hyporesponsiveness or insensitivity to the antidiuretic action of arginine vasopressin (AVP). The principal cell-specific water channel aquaporin-2 [...] Read more.

As a rare hereditary disease, congenital nephrogenic diabetes insipidus (NDI) is clinically characterized by polyuria with hyposthenuria and polydipsia. NDI results from collecting duct principal cell hyporesponsiveness or insensitivity to the antidiuretic action of arginine vasopressin (AVP). The principal cell-specific water channel aquaporin-2 (AQP2) plays an essential role in water reabsorption along osmotic gradients. The capacity to accumulate AQP2 in the apical plasma membrane in response to decreased fluid volume or increased plasma osmolality is critically regulated by the antidiuretic hormone AVP and its receptor 2 (AVPR2). Mutations in AVPR2 result in X-linked recessive NDI, the most common form of inherited NDI. Genetic defects in AQP2 cause autosomal recessive or dominant NDI. In this review, we provide an updated overview of the genetic and molecular mechanisms of congenital NDI, with a focus on the potential disease-causing mutations in AVPR2 and AQP2, the molecular defects in the AVPR2 and AQP2 mutants, post-translational modifications (i.e., phosphorylation, ubiquitination, and glycosylation) and various protein-protein interactions that regulate phosphorylation, ubiquitination, tetramerization, trafficking, stability, and degradation of AQP2. Full article

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23 pages, 2575 KiB

Open AccessFeature PaperReview

Insight into Salivary Gland Aquaporins

by Claudia D’Agostino, Osama A. Elkashty, Clara Chivasso, Jason Perret, Simon D. Tran and Christine Delporte

Cells 2020, 9(6), 1547; https://doi.org/10.3390/cells9061547 - 25 Jun 2020

Cited by 39 | Viewed by 8559

Abstract

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according [...] Read more.

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia. Full article

(This article belongs to the Special Issue Advances in Aquaporins)

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