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Cellular changes in carcinomas include alterations in cell proliferation, cell migration, cell-cell adhesion, and cellular polarity. In vitro studies have revealed that the water channels, aquaporin-1 (AQP1) and AQP3, can influence cell migration and cell-cell adhesion. Of note, we previously showed that AQP1 overexpression reduced levels of cell-cell adhesion proteins, whereas AQP3 increased levels when overexpressed in normal epithelial cells. Expression of AQP1 and AQP3 in breast carcinoma is associated with lymph node metastasis, recurrence, and poor survival of patients with breast cancer. In this study, we investigated if AQP1 and AQP3 affected cell polarity in breast cancer by studying the relationship between the major polarity protein Scribble and AQP1 and AQP3. In breast cancer tissue samples, the protein expression of AQP1, AQP3, and Scribble did not show an obvious correlation. However, in a GST pull-down assay, AQP1 and AQP3 interacted with Scribble. AQP1 overexpression reduced the size of 3D spheroids as well as reduced Scribble levels at cell-cell contacts, whereas AQP3 overexpression showed no significant change in spheroid size compared with control, AQP3 overexpression also reduced Scribble levels at cell-cell contacts. Of note, AQP1 overexpression increased cell migration and induced cell detachment and dissemination from migrating breast cancer cell sheets, whereas AQP3 overexpression did not. Thus, AQP1 and AQP3 differentially affect 3D-grown breast cancer spheroids, and especially AQP1 may contribute to cancer development and spread via negatively affecting cellular junctions and cell polarity proteins as well as increasing cell migration and cell detachment. NEW & NOTEWORTHY Overexpression of the water channels aquaporin-1 and aquaporin-3 reduced levels of the key polarity protein Scribble at cell-cell junctions, suggesting potential implications in breast cancer progression and metastasis.

Aquaporins play a crucial role in water homeostasis in the human body, and recently the physiological importance of aquaporins as glycerol channels have been demonstrated. The aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) represent key glycerol channels, enabling glycerol flux across the membranes of cells. Adipocytes are the major source of glycerol and during lipolysis, glycerol is released to be metabolized by other tissues through a well-orchestrated process. Here we show that both AQP3 and AQP7 bind to the lipid droplet protein perilipin 1 (PLIN1), suggesting that PLIN1 is involved in the coordination of the subcellular translocation of aquaglyceroporins in human adipocytes. Moreover, in addition to aquaglyceroporins, we discovered by transcriptome sequencing that AQP1 is expressed in human primary adipocytes. AQP1 is mainly a water channel and thus is thought to be involved in the response to hyper-osmotic stress by efflux of water during hyperglycemia. Thus, this data suggests a contribution of both orthodox aquaporin and aquaglyceroporin in human adipocytes to maintain the homeostasis of glycerol and water during fasting and feeding., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Decreased expression of the renal aquaporin (AQP) protein family is associated with hydronephrosis in adult humans and animals. However, the expression of AQPs, especially subtypes AQP1-3, which play a core role in the urinary concentration function, in hydronephrotic human fetuses is not clear. The aim of this study is to investigate the expression of the AQP1-3 in normal and hydronephrotic human fetal kidneys., Methods: Twenty-one normal and six hydronephrotic kidney (HK) samples were harvested from abortive fetuses. Meanwhile, seven normal adult human kidney samples were collected as positive controls. Quantitative real-time PCR, western blotting, and immunohistochemistry were used to analyze the expression of AQP1-3., Results: Both the protein and messenger mRNA expression levels of AQP1-3 increased with gestational age in the normal fetuses, but the levels were significantly lower than those in the adult tissues and significantly higher than those in the hydronephrotic fetuses at the same gestational age., Conclusions: The increased expression of AQP1-3 with gestational age in the fetal kidney may indicate maturation of the urinary concentrating ability. The lower expression of AQP1-3 in HKs may reflect a maturation obstacle with regard to urinary concentration in human hydronephrotic fetuses.

Aquaporins (AQPs) facilitate transmembrane water and solute transport, and in addition to contributing to transepithelial water transport, they safeguard cell volume homeostasis. This study examined the expression and localization of AQP1 and AQP3 in the gills of Japanese medaka ( Oryzias latipes) in response to osmotic challenges and osmoregulatory hormones, cortisol, and prolactin (PRL). AQP3 mRNA was inversely regulated in response to salinity with high levels in ion-poor water (IPW), intermediate levels in freshwater (FW), and low levels in seawater (SW). AQP3 protein levels decreased upon SW acclimation. By comparison, AQP1 expression was unaffected by salinity. In ex vivo gill incubation experiments, AQP3 mRNA was stimulated by PRL in a time- and dose-dependent manner but was unaffected by cortisol. In contrast, AQP1 was unaffected by both PRL and cortisol. Confocal microscopy revealed that AQP3 was abundant in the periphery of gill filament epithelial cells and co-localized at low intensity with Na + ,K + -ATPase in ionocytes. AQP1 was present at a very low intensity in most filament epithelial cells and red blood cells. No epithelial cells in the gill lamellae showed immunoreactivity to AQP3 or AQP1. We suggest that both AQPs contribute to cellular volume regulation in the gill epithelium and that AQP3 is particularly important under hypo-osmotic conditions, while expression of AQP1 is constitutive.

Background: Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available biomarkers for the diagnosis, prediction of prognosis, and target therapy have not yet been identified., Objective: To investigate the expression of aquaporin-1 (AQP1) and AQP3 protein and their clinicopathological significances in PDACs., Materials and Method: AQP1 and AQP3 protein expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues was measured by immunohistochemistry., Results: Western blot showed that AQP1 and AQP3 protein expression was significantly higher in PDAC tissues than that in benign pancreatic tissues (P<0.01). Immunohistochemistry showed that the percentages of positive AQP1 and AQP3 expressions were significantly higher in PDAC tumors than that in peritumoral tissues, benign, and normal pancreatic tissues (P<0.01). Benign pancreatic lesions with positive AQP1 and AQP3 expression exhibited a dysplasia or intraepithelial neoplasia. The percentage of cases with positive AQP1 and AQP3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion, and having low Tumor, Node and Metastasis (TNM) stage disease than in patients with lymph node metastasis, invasion, and high TNM stage disease (P<0.05 or <0.01). Kaplan-Meier survival analysis showed that positive AQP1 and AQP3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive AQP1 and AQP3 expression was independent poor prognosis factors in PDAC patients. The area under the curve of receiver operating characteristic curve was 0.669 for AQP1 and 0.707 for AQP3, respectively., Conclusions: Positive AQP1 and AQP3 expressions are associated with the tumorigenesis and progression of PDAC. Both AQP1 and AQP3 are a diagnostic marker of PDAC and a predictive marker of poor prognosis in PDAC patients.

Chondrocytes are cells of articular cartilage particularly sensitive to water transport and ionic and osmotic changes from extracellular environment and responsible for the production of the synovial fluid. Aquaporins (AQPs) are a family of water and small solute transport channel proteins identified in several tissues, involved in physiological pathways and in manifold human diseases. In a recent period, AQP1 and 3 seem to have a role in metabolic water regulation in articular cartilage of load bearing joints. The aim of this study was to examine the levels of AQP1 and 3 during the chondrogenic differentiation of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT). For the determination of chondrogenic markers and AQPs levels, glycosaminoglycans (GAGs) quantification, immunocytochemistry, RT-PCR, and Western blot were used after 0, 7, 14, 21, and 28 days from the start of differentiation. At 21 days, chondrocytes derived from AT-MSCs were able to produce augmented content of GAGs and significant quantity of SOX-9, lubricin, aggrecan, and collagen type II, suggesting hyaline cartilage formation, in combination with an increase of AQP3 and AQP1. However, while AQP1 level decreased after 21 days; AQP3 reached higher values at 28 days. The expression of AQP1 and 3 is a manifestation of physiological adaptation of functionally mature chondrocytes able to respond to the change of their internal environment influenced by extracellular matrix. The alteration or loss of expression of AQP1 and 3 could contribute to destruction of chondrocytes and to development of cartilage damage., (© 2017 Wiley Periodicals, Inc.)

Objective: Our research was to detect the expression of aquaporins. NF-κB in Irritable bowel syndrome (IBS) rat models' colon so as to find novel pathogenesisof IBS., Results: The expression of AQP1, AQP3, and AQP8 of IBS model group was down-regulated while NF-κB p65 was up-regulated comparing with control group (p < 0.05), and the expression of AQP1, AQP3, and AQP8 of inhibitor group was up-regulated while NF-κB p65 was down-regulated comparing with IBS model group (p < 0.05)., Materials and Methods: 18 adult female SD big rats were divided into three groups:the rats in control group were normal rats,the rats in IBS model group and the rats of inhibitor group were injected with the inhibitor of NF-κB (PDTC). Immunohistochemical technique and western blot were performed to detect the expression of AQP1, AQP3, AQP8 and NF-κB p65. RT-PCR was performed to detect the expression of AQP1, AQP3, and AQP8., Conclusions: Liquid water metabolic abnormalities and intestine permeability alteration might be the mechanism of IBS by down-regulating AQP1, AQP3 and AQP8 via NF-κB pathway.

Senescence-associated alterations in structure and function of cornea make it more sensitive to traumas and disease. Trauma of cornea leads to edema and vision impairment and only corneal transplantation remains the effective for vision correction. Role of aquaporins for cornea endothelium function, as well as age-related changes of their activity, are not entirely understood. Herein, we studied changes with age the water permeability (Pf) of the plasma membranes of the corneal endothelial cells and the level of expression in them of the mRNA genes of the water channels of the aquaporins AQP1 and AQP3 in Wistar and senescence-accelerated OXYS rats. From the age of 3 to 18 months, Pf in Wistar rats increased, in OXYS - decreased and was twice lower than in Wistar rats. The expression of aqp1 mRNA (studied by RT-PCR) in the endothelium was the same in Wistar and OXYS rats at the age of 3 months. By the age of 18 months, it increased only in Wistar rats and became twice higher than in OXYS rats. The expression of aqp3 mRNA in the endothelium of 3-month-old OXYS rats was half that of Wistar rats and did not change with age, while in Wistar rats it decreased and at 18 months was 4 times lower than in 3 months. We supposed that increased water permeability of endothelial cells in Wistar rats is adaptive and compensates for the decrease in endothelial cell density with age, while the accelerated aging of OXYS rats abolishes this compensation.

Aquaporins (AQPs ) mediate water flux between the four distinct water compartments in the central nervous system (CNS). In the present chapter, we mainly focus on the expression and function of the 9 AQPs expressed in the CNS, which include five members of aquaporin subfamily: AQP1, AQP4, AQP5, AQP6, and AQP8; three members of aquaglyceroporin subfamily: AQP3, AQP7, and AQP9; and one member of superaquaporin subfamily: AQP11. In addition, AQP1, AQP2 and AQP4 expressed in the peripheral nervous system (PNS) are also reviewed. AQP4, the predominant water channel in the CNS, is involved both in the astrocyte swelling of cytotoxic edema and the resolution of vasogenic edema, and is of pivotal importance in the pathology of brain disorders such as neuromyelitis optica , brain tumors and Alzheimer's disease. Other AQPs are also involved in a variety of important physiological and pathological process in the brain. It has been suggested that AQPs could represent an important target in treatment of brain disorders like cerebral edema. Future investigations are necessary to elucidate the pathological significance of AQPs in the CNS.

The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

The association between the expression of aquaporins (AQPs) in kidney tissues and the occurrence of edema in nephrotic syndrome (NS) remains unclear. The current study aimed to investigate this association. A total of 54 patients with primary glomerular disease, diagnosed by renal biopsy, were divided into three groups: Control, NS without edema and NS with edema. The expression of AQP1, AQP2, AQP3 and AQP4 in kidney tissues from these patients was assessed using immunohistochemistry, and urinary AQP concentrations were quantified by ELISA. Comparison of the three groups was conducted using one way analysis of variance, independent samples t‑test or the Chi‑square test. AQP1 was strongly expressed in the proximal tubules. The proportion of the AQP1‑positive area in kidney tissues from patients with NS with edema was significantly reduced, in comparison with the other two groups. By contrast, the proportion of the AQP2‑positive area in the NS with edema group was significantly higher than that of the other two groups; significant differences were also observed between the control and NS without edema groups for this parameter. Urinary AQP2 concentrations in patients with NS (with and without edema) were significantly higher than that of the control group, and exhibited a significant positive correlation with kidney tissue AQP2 concentrations. The present study demonstrated the abnormal expression pattern of AQP1‑AQP4 in the kidney tissues of patients with NS, providing a basis for an improved understanding of the role of AQP in the pathogenesis of NS.

Lumbar intervertebral disc degeneration is induced by multiple factors, but few studies have examined the effects of aquaporins on this process. We compared the expression levels of aquaporins 1 and 3 in normal and degenerative lumbar intervertebral discs. Fifteen normal and 15 degenerative lumbar intervertebral disc tissues were excised from lumbar burst fracture patients during orthopedic operations at the Dali College subsidiary hospital. Tissues were stained with hematoxylin-eosin and the expression levels of aquaporins 1 and 3 were measured by immunohistochemistry. Hematoxylin-eosin-staining results illustrated that the structures of the intervertebral disc tissues from the control group were clear, with distinct collagen fiber shapes and slight edema but without mucoid degeneration. Structures of the intervertebral disc tissues from the disease group were obscure and disordered with hyperplastic collagen fibers and tissues of severe inflammatory edemas with necrosis mucoid degeneration. Immunohistochemistry results demonstrated that the average absorbances of aquaporins 1 and 3 in the disease group were significantly lower than those in the control group (P < 0.01), suggesting that the reduction of aquaporins 1 and 3 may be a factor resulting in lumbar intervertebral disc degeneration.

Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins (AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and -8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1, -4, and -8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.

Background: Overexpression of several aquaporins has been reported in different types of human cancer but the role of aquaporins in carcinogenesis has not yet been clearly defined. There is few report concerning role of aquaporins in human cervical carcinogenesis so far. Here, we determined the expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in Chinese women of Uygur ethnicity., Methods and Results: Real-time PCR analyses demonstrated aquaporin 1, 3 mRNA were differentially expressed in cervical carcinoma, CIN 2-3 and mild cervicitis. Immunofluorescent and immunohistochemical analyses demonstrated aquaporin 1 was predominantly localized to stromal endothelial cells in cervical lesions. Aquaporin 3 was localized to the membrane of normal squamous epithelium, CIN and carcinoma cells. Aquaporin 1 and 3 were upregulated in cervical cancer compared to mild cervicitis and CIN2-3 (P<0.05); Tumor expression of aquaporin 1, 3 significantly increased in advanced stage disease, and patients with deeper tumor infiltration, lymph node metastases or larger tumor volume (P<0.05). Multivariate analysis demonstrated that aquaporin 1, 3 were not independent prognostic factors in cervical carcinoma., Conclusion: Aquaporins may participate in the initiation and progression of cervical carcinoma by promoting tumor growth, invasion or lymph node metastasis. Further study is required to determine whether aquaporins have potential as prognostic factors in cervical cancer.

Objective: To observe the effect of acetazolamide (AZ) on the expressions of aquaporin 1 (AQP1) and AQP3 in fibroblast-like synoviocytes of rheumatoid arthritis (RAFLSs) and explore the roles of AQP1 and AQP3 in the development of rheumatoid arthritis (RA)., Methods: The study included 12 RA with knee hydrarthrosis and 10 osteoarthritis (OA) with knee hydrarthrosis and collected their synovia. From the synovia, FLSs were separated and cultured in vitro. RAFLSs were treated with different concentrations of acetazolamide (10(-4), 10(-6), 10(-8) mol/L) for different time (24, 48, 72 hours). The expressions of AQP1 mRNA and AQP3 mRNA in RAFLSs and OAFLSs were measured by RT-PCR; the expression of AQP1 protein was detected by immunofluorescence in RAFLSs and OAFLSs treated with the same concentration of acetazolamide (10(-4) mol/L) for different time (24, 48, 72 hours)., Results: AQP1 mRNA and AQP3 mRNA were both expressed in RAFLSs. The level of AQP1 mRNA in RAFLSs was significantly higher than that in OAFLSs (P<0.05). Different concentrations of acetazolamide (10(-4), 10(-6), 10(-8) mol/L) were able to significantly decrease the expression level of AQP1 mRNA in RAFLSs (P<0.05) in a time- and dose-dependent manner. There was no significant difference in transcription level of AQP3 mRNA between RAFLSs and OAFLSs (P>0.05); Immunofluorescence showed that AQP1 protein was significantly distributed on cell membrane. AQP1 protein expression was very apparent without acetazolamide treatment, whereas the expression was significantly attenuated by acetazolamide in a time-dependent manner., Conclusion: Up-regulation of AQP1 expression in RA synovial membrane may be the one of mechanisms of arthroedema. Acetazolamide can reduce the expression of AQP1 rather than AQP3 in RAFLSs.

Overexpression of several aquaporins (AQPs) has been reported in different types of human cancer but their role in carcinogenesis, for example in the cervix, have yet to be clearly defined. In this study, expression of AQPs in cervical carcinomawas investigated by real-time PCR, immunofluorescent and immunohistochemical assays and evaluated for correlations with clinicopathologic variables. AQP1, 3, 8 exhibited differential expression in cervical carcinoma, corresponding CIN and mild cervicitis. AQP1 was predominantly localized in the microvascular endothelial cell in the stroma of mild cervicitis, CIN and cervical carcinoma. AQP3 and AQP8 were localized in the membrane of normal squamous epithelium and carcinoma cells, local signals being more common than diffuse staining. AQP1 and AQP3 expression was remarkably stronger in cervical cancer than in mild cervicitis and CIN2-3 (P<0.05). AQP8 expression was highest in CIN2-3 (91.7%), but levels in cervical carcinoma were also higher than in mild cervicitis. AQP1, AQP3, AQP8 expression significantly increased in advanced stage, deeper infiltration, metastatic lymph nodes and larger tumor volume (P<0.05). Our findings showed that AQPs might play important roles in cervical carcinogenesis and tumour progression in Uygur women.

Objective: To investigate the expressions of aquaporins (AQPs) in the mouse prostatic tissue and their significance, and to provide some evidence for a deeper insight into the physiological function and regulation of AQP expressions in normal and diseased prostatic tissues., Methods: The mRNA expressions of AQP0 - 4 in the mouse prostatic tissue were determined by RT-PCR, and the expressions and localizations of AQP1 and AQP3 proteins were characterized by Western blot and immunohistochemistry., Results: RT-PCR exhibited the mRNA expressions of AQP1 and AQP3, but not those of AQP0, AQP2 and AQP4 in the prostate tissue, while Western blot showed the expression of the AQP1 protein with the relative molecular mass (RMM) of 28 000 and those of the glycosylated and non-glycosylated AQP3 proteins with the RMM of 35 000 and 27 000, respectively. Immunohistochemistry indicated the strong expression of AQP1 in the cyst and plasma membrane of the secretary cells and that of AQP3 in the stroma cells of the prostate., Conclusion: The AQP1 and AQP3 genes were expressed in the secretary epithelia of the mouse prostate tissue, which suggests that AQP1 and AQP3 may play an important role in the secretion of prostatic fluid.

An oncogenic capacity of aquaporins, transmembrane channels for water, was recently proposed. This study seeks to elucidate the involvement of aquaporin 1, 3, and 5 in the development and progression of lung cancer. Expression of aquaporin 1, 3, and 5 was examined by immunohistochemistry, Western blot, and laser-captured microdissection/real-time reverse transcription polymerase chain reaction in 160 lung cancers of various histologic subtypes; and its correlation with clinicopathological factors and survival was analyzed. Aquaporin 1, 3, and 5 were expressed in tumor cells in 71%, 40%, and 56% of lung cancers, respectively. Aquaporin expressions were frequent in adenocarcinomas, whereas aquaporin 1 and 5 were negative in squamous cell carcinomas. Bronchioloalveolar carcinoma cells exhibited an apicolateral aquaporin 1 and apicolateral or basolateral aquaporin 3 localization in nonmucinous type, and apical aquaporin 1 and 5 and basolateral aquaporin 3 expression in mucinous type, which corresponded to aquaporins expression of nonneoplastic lung tissue. Basolateral aquaporin 5 expression was acquired during tumorigenesis of nonmucinous bronchioloalveolar carcinoma. In contrast, invasive adenocarcinoma tumor cells overexpressed aquaporin 1 and 5 with loss of subcellular polarization and with an intracytoplasmic distribution. Overexpression of aquaporin 1 correlated with high postoperative adenocarcinoma metastasis ratios and unfavorable disease-free survival rates (P = .031). We conclude that expression patterns of aquaporin 1, 3, and 5 in lung cancer cells are mostly associated with cellular differentiation. However, the expression of aquaporin 1 and 5 is up-regulated in invading lung cancer cells, particularly in adenocarcinomas; and the overexpression of aquaporin 1 with loss of subcellular polarization is suggested to be involved in their invasive and metastatic potential., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Menière's Disease (MD) is an episodic cochleovestibular dysfunction of unknown etiology, still lacking a specific test and therapy. The proposed theories on the pathophysiology include genetic factors and factors relating to inner ear homeostasis. Various aquaporins (AQP), water channels, expressed in the inner ear and the vestibular organ, are involved in homeostasis. Mutations in AQP genes could result in disturbed inner ear homeostasis and endolymphatic hydrops, and therefore be involved in the pathogenesis of MD., Aim: To search for mutations in AQP1 to 4 in patients suffering from MD., Methods: In patients with definite MD, DNA was extracted from whole blood. The coding sequences of AQP1 to 4 were amplified by PCR reaction and sequenced., Results: One sequence alteration, homozygous c.105G->C (conservative change without alteration of amino acid) in AQP3 was detected in 11 out of 34 patients but not in 100 control chromosomes., Conclusion: By itself the detected alteration is unlikely to play a role in the pathogenesis of MD. However, together with an additional modifying gene an effect can not be excluded. Additional regions (introns, splice-sites) and other genes involved in inner ear homeostasis need to be analyzed to identify a possible molecular alteration in MD., (Copyright © 2010 S. Karger AG, Basel.)

Background: Over 70% of the total tissue weight in the cartilage matrix consists of water, and the early-stage osteoarthritic cartilage is characterized by swelling. Water transport in the cartilage matrix and across the membranes of chondrocytes may be important in normal and pathological conditions of cartilage. The purpose of this study was to identify aquaporin-1 (AQP1) and aquaporin-3 (AQP3) expressions in the mandibular condylar cartilage after experimentally induced osteoarthritis (OA) in rats., Methods: An experimental temporomandibular joint OA was induced by partial discectomy in rats. The pathological characteristics of the normal, early-stage, and late-stage osteoarthritic TMJ cartilages were verified by histological techniques. The AQP1 and AQP3 gene expressions in the normal and osteoarthritic cartilages were measured using quantitative real-time reverse-transcription PCR analysis. The cartilage sections were incubated in primary polyclonal antibodies to AQP3; immunofluorescent microscopy was used to examine the AQP3 expression shown by its protein level., Results: The mRNA expression levels of AQP1 and AQP3, analyzed using quantitative PCR, revealed that AQP3 mRNA was highly up-regulated in the OA cartilage, which was considered significant. There was no notable difference in the expression of AQP1 mRNA between OA and normal controls. With the progressing of the OA, the localization of the AQP3 protein was quite different from that of the normal cartilage. Compared to the normal cartilage, the expressions of AQP3 protein were observed mainly in the proliferative zone and the upper mid-zone chondrocytes at the early-stage of OA, and were observed to appear frequently throughout the mid- and deep zone during the late-stage of OA., Conclusions: The high expression of AQP3 mRNA in the OA cartilage and the different localization of the AQP3 protein suggest that it may play a particular role in OA pathogenesis. Further study of AQP3 function may provide new insight into the understanding of the molecular mechanisms underlying OA.

Euryhaline fish possess the ability to compensate for environmental salinity changes through hydro-mineral regulation. A number of proteins have been studied in order to understand water and ion exchanges, known as fish osmoregulation. Sea-bass (Dicentrarchus labrax) cDNA sequences encoding a homologue of mammalian aquaporin (termed AQP1) and a homologue of mammalian aquaglyceroporin (termed AQP3) have been isolated and sequenced. The aquaporin amino acid sequences share respectively more than 60% and 65% identity with other known aquaporins. We have shown that salinity influences aquaporin expression levels in the gill, kidney and digestive tract, the main osmoregulatory organs. AQP1 may have a major osmoregulatory role in water transport in kidney and gut in SW-acclimated fish, whereas AQP3 could be implicated in gill water transport in FW-acclimated fish.

Aquaporin-1 (AQP1) and aquaporin-3 (AQP3) water channels expressed in the kidney play a critical role in the urine concentrating mechanism. Mice with AQP1 or AQP3 deletion have a urinary concentrating defect. To better characterize this defect, we studied the influence of an acute urea load (300 mumol ip) in conscious AQP1-null, AQP3-null, and wild-type mice. Urine was collected and assayed every 2 h, from 2 h before (baseline) to 8 h after the urea load. Mice of all genotypes excreted the urea load in approximately 4 h with the same time course. Interestingly, despite their low baseline, the AQP3-null mice raised their urine osmolality and urea concentration progressively after the urea load to values almost equal to those in wild-type mice at 8 h. In contrast, urine non-urea solute concentration did not change. Urine volume fell in the last 4 h to about one-fourth of basal values. AQP1-null mice increased their urine flow rate much more than AQP3-null mice and showed no change in urine osmolality and urea concentration. The urea load strongly upregulated urea transporter UT-A3 expression in all three genotypes. These observations show that the lack of AQP3 does not interfere with the ability of the kidney to concentrate urea but impairs its ability to concentrate other solutes. This solute-selective response could result from the capacity of AQP3 to transport not only water but also urea. The results suggest a novel role for AQP3 in non-urea solute concentration in the urine.