1.Association study of single nucleotide polymorphisms of AQP7 and AQP9 genes with type 2 diabetes mellitus among ethnic Han Chinese population.
Siqi HE ; Man YANG ; Ying YANG ; Feiying WANG ; Xiaoling WANG ; Tinglian LU ; Ming JIAO ; Yiping LI
Chinese Journal of Medical Genetics 2022;39(2):234-239
OBJECTIVE:
To assess the association of single nucleotide polymorphisms (SNP) of aquaporin 7 ( AQP7) and aquaporin 9 ( AQP9) genes and type 2 diabetes mellitus (T2DM) among ethnic Han Chinese population.
METHODS:
A case-control study involving 1194 subjects with T2DM and 1274 non-diabetic mellitus (NDM) subjects were enrolled. Genotypes of three SNPs (rs3758269 of AQP7 gene, rs16939881 and rs57139208 of AQP9 gene) were determined by using a MassArray method. The association of the three SNPs with T2DM was assess, and the correlation of glucose and lipid metabolism parameters with various SNP genotypes in the NDM group was analyzed.
RESULTS:
The allelic and genotypic frequencies of the three SNPs did not differ significantly between the two groups (P>0.05). Nor was there significant difference between the two groups with different genetic models (P>0.05). No significant association of genotypes of AQP7 gene rs3758269, AQP9 gene rs16939881 and rs57139208 with glucose and lipid metabolism parameters were observed in the NDM group (P>0.05).
CONCLUSION
The rs3758269 in AQP7 gene and rs16939881 and rs57139208 in AQP9 gene are not associated with the genetic susceptibility of T2DM among ethnic Han Chinese population.
Aquaporins/genetics*
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Case-Control Studies
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China
;
Diabetes Mellitus, Type 2/genetics*
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Genetic Predisposition to Disease
;
Humans
;
Polymorphism, Single Nucleotide
2.Transcatheter delivery of recombinant adenovirus vector containing exogenous aquaporin gene in treatment of Sjögren's syndrome.
Hong HE ; Jieqiong ZHANG ; Yan FAN ; Xiaoshuang SUN ; Yuhao ZHU
Journal of Zhejiang University. Medical sciences 2016;45(1):86-97
Sjögren's syndrome is a kind of autoimmune disease, whose main clinical symptoms are dry mouth, dry eye and chronic parotid glandular inflammation. The conservative treatments include artificial tears or saliva,oral administration of corticosteroids,and immunosuppressantsl with limited effectiveness. Along with the development of molecular biology, vast attentions are being paid to researches on gene therapy for Sjögren's syndrome, hopefully to bring gospel to patients with Sjögren's syndrome. This article reviews the recent research progresses on transcatheter delivery of recombinant adenovirus vector with aquaporin gene in experimental treatment of Sjögren's syndrome.
Adenoviridae
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Aquaporins
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genetics
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Autoimmune Diseases
;
therapy
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Catheters
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Genetic Therapy
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Genetic Vectors
;
administration & dosage
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Humans
;
Sjogren's Syndrome
;
therapy
3.Effects of electroacupuncture on cochlea morphology and expression of aquaporins in guinea pigs with endolymphatic hydrops.
Liyuan JIANG ; Canjun WANG ; Fangying NI ; Huade CHEN
Chinese Acupuncture & Moxibustion 2015;35(6):579-584
OBJECTIVETo observe the effects of electroacupuncture (EA) on cochlea morphology and expression of aquaporin 1 (AQP1) in guinea pigs with endolymphatic hydrops, so as to explore the possible mechanism of EA on endolymphatic hydrops.
METHODSForty guinea pigs were randomly divided into a blank group, a model group, a medication group and an EA group, 10 guinea pigs in each one. Model of endolymphatic hydrops was established by using intraperitoneal injection of aldosterone. Guinea pigs in the blank group and model group were treated with identical immobilization as EA group but no treatment was given; guinea pigs in the medication group were treated with intragastric administration of hydrochlorothiazide at a dose of 5 mg/kg, once a day for consecutive 10 days; guinea pigs in the EA group were treated with' EA at "Baihui" (GV 20) and "Tinggong"(SI 19), once a day for consecutive 10 days. The serum ionic concentration in each group was tested by turbidimetric method; hematoxylin-eosin staining was used to measure the severity of cochlea hydrops; immunohistochemical method was used to observe the expression of AQP1 in the cochlea.
RESULTS(1) There was no endolymphatic hydrops in the blank group, moderate-severe endolymphatic hydrops in the model group and slight endolymphatic hydrops in the EA group and medication group. (2) The concentration of K+ and Ca2+ in the EA group was higher than that in the model group and medication group (all P<0. 01); the concentration of Na+ was lower than that in the model group (P< 0. 01) but higher than that in the medication group (P<0. 01); the concentration of Cl- was higher than that in the medication group (P<0. 01), but not significantly different from the model group (P>0. 05). (3) The ratio of expression area of AQP1 in the model group was lower than that in the blank group (P<0. 01); the ratio of expression area of AQP1 in the EA group was higher than that in the model group (P<0. 01), and lower than that in the medication group without significant difference (P>0. 05).
CONCLUSIONEA could relieve the endolymphatic hydrops in guinea pigs; the mechanism is likely to be related with up-regulating the expression of AQP1 in cochlea and ion concentration might be an important factor involved.
Animals ; Aquaporins ; genetics ; metabolism ; Cochlea ; anatomy & histology ; metabolism ; Disease Models, Animal ; Electroacupuncture ; Endolymphatic Hydrops ; genetics ; metabolism ; therapy ; Guinea Pigs ; Humans ; Male
4.Relationship between efficacy exertion of diuretic traditional Chinese medicines and aquaporin.
Peng-cheng WANG ; Shan ZHAO ; Qiu-hong WANG ; Hai-xue KUANG
China Journal of Chinese Materia Medica 2015;40(12):2272-2277
In recent years, the discovery and studies on aquaporin have made us have a more in-depth understanding about the physiological and pathological processes of water metabolism. Over years, however, there has been no quantitative study on the target sites of diuretic traditional Chinese medicines at the molecular level. In that case, aquaporin was found to been a new target molecule to explain the efficacy exertion of diuretic traditional Chinese medicines. By studying aquaporin, researchers can understand the implicit meaning of the diuretic effect of traditional Chinese medicines and conduct quantitative studies on the diuretic effect. So far, many scholars have conducted a series of studies in the traditional Chinese medicine field by using the findings on aquaporin and made certain advances. This article provides a summary about the efficacy exertion of diuretic traditional Chinese medicines through target molecule aquaporin.
Animals
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Aquaporins
;
genetics
;
metabolism
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Diuretics
;
pharmacology
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Drugs, Chinese Herbal
;
pharmacology
;
Humans
;
Medicine, Chinese Traditional
;
Water
;
metabolism
5.Construction of short hairpin RNA targeting aquaglyceroporin 9 and screening its effect on molecular mechanisms of nonalcoholic fatty liver disease using a cell model system.
Chuan WANG ; Yu-jun KANG ; Zheng JIANG ; Pi-long WANG
Chinese Journal of Hepatology 2013;21(3):222-227
OBJECTIVETo construct a short hairpin (sh)RNA targeting aquaglyceroporin 9 (AQP9) that effectively silences gene expression in liver cells in order to investigate of the role of AQP9 in nonalcoholic fatty liver disease (NAFLD) pathogenesis using an in vitro cell model system.
METHODSSmall interfering (si)RNAs were designed against the human gene sequences encoding AQP9 (NCBI GenBank Accession No. AB008775) and unrelated control sequences, synthesized, annealed to form double-strands, and inserted into the pGenesil- 1 shRNA-expression plasmid. The silencing effects of the four pshRNA-AQP9 constructs (a-d) and the pshRNA-negative control construct were investigated by transfecting into the L02 human normal liver cell line and detecting expression of AQP9 mRNA and protein (relative to beta-actin) by reverse transcription-PCR and western blotting. The NAFLD cell model was established by treating L02 cells with oleic acid to induce fatty degeneration. After transfecting the NAFLD cell model with various constructs, the effects on NAFLD-related features were investigated by staining with Oil Red O (to detect lipid droplets) and performing enzymatic assays (to quantitate triglyceride (TG), free fatty acid (FFA) and glycerol content). The significance of intergroup differences was assessed by analysis of variance test.
RESULTSOf the four pshRNA-AQP9 constructs, pshRNA-AQP9a produced the most robust silencing effect on AQP9 mRNA (25.1 - 1.2% vs. untransfected: 39.3 +/- 1.7% and pshRNA-negative control: 39.4 +/- 1.5%, P < 0.01) and protein (25.4 - 2.0% vs. untransfected: 35.1 +/- 1.9% and psh-RNA-negative control: 35.6 +/- 2.3%, P < 0.01). Oleic acid-induced L02 cells showed enhanced AQP9 mRNA and protein expression, and increased intracellular content of lipid, TG, FFA, and glycerol, which were significantly reduced by pshRNA-AQP9a transfection (all P <0.05).
CONCLUSIONThe new pshRNA-AQP9a construct can efficiently reduce AQP9 expression in cultured human liver cells and relieve steatosis-related features in an NAFLD cell model, pshRNA-AQP9a represents a novel tool for studying the role ofAQP9 in NAFLD pathogenesis and its potential as a gene therapy strategy.
Aquaporins ; genetics ; Cell Line ; Fatty Liver ; genetics ; Gene Expression ; Genetic Vectors ; Hepatocytes ; metabolism ; Humans ; Non-alcoholic Fatty Liver Disease ; Plasmids ; RNA Interference ; RNA, Messenger ; RNA, Small Interfering
6.Aquaporin 8 expression is reduced and regulated by microRNAs in patients with ulcerative colitis.
Min MIN ; Li-hua PENG ; Gang SUN ; Ming-zhou GUO ; Ze-wu QIU ; Yun-sheng YANG
Chinese Medical Journal 2013;126(8):1532-1537
BACKGROUNDUlcerative colitis (UC) is associated with differential expression of genes involved in inflammation and tissue remodeling. MicroRNA (miRNA) plays an important role in the pathogenesis of UC by regulating the gene expression at the post-transcriptional level and control crucial physiological processes. This study aimed to identify aquaporin 8 (AQP8) expression and its relationship with miRNA in UC patients.
METHODSHuman colon samples, in this study, were obtained from 20 patients with UC and 16 healthy subjects undergoing diagnostic colonoscopy at the Chinese People's Liberation Army General Hospital between December 2009 and June 2010. We screened different genes from UC tissues and healthy subjects using genome-wide microarray, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Regulation of gene expression by miRNAs was assessed by luciferase reporter construct assays and transfection of specific miRNA mimics and inhibitor.
RESULTSWe identified that 1596 genes were increased and 1301 genes were decreased in UC patients compared to healthy subjects. Among them, we focused on the analysis of AQP8 which was decreased three folds in UC tissues (P < 0.01). The expression of AQP8 mRNA and protein were decreased in UC tissue and tumor necrosis factor (TNF)-α treated HT29 cells compared with controls (P < 0.05). We searched candidate target miRNAs of AQP8 through bioformatics and the luciferase report assay analysis indicated that miR-424, miR-195, miR-330, miR-612, and miR-16 which has complementary site in the 3-untranslated region (3'UTR) of AQP8 could decrease the relative luciferase activities by 10% - 45%.
CONCLUSIONAQP8 and its relationship with miRNAs may be involved in the pathogenesis of UC.
Adult ; Aged ; Aquaporins ; genetics ; Colitis, Ulcerative ; genetics ; Female ; Gene Expression Regulation ; HT29 Cells ; Humans ; Male ; MicroRNAs ; physiology ; Middle Aged ; Tumor Necrosis Factor-alpha ; pharmacology
7.Effects of acupoint area and non-acupoint area of eye-acupuncture on expressions of VIP and AQP 8 in colonic tissues in rats with D-IBS.
Hui-Hui LIU ; Xu-Dong LIU ; Yan-Jie WANG ; Hong-Quan GUAN ; Ji-Yan CHAI ; Jin-Ru ZHAO ; De-Shan WANG
Chinese Acupuncture & Moxibustion 2012;32(10):919-924
OBJECTIVETo explore the point specificity of eye-acupuncture and the mechanism of eye-acupuncture on diarrhea-predominant irritable bowel syndrome (D-IBS).
METHODSForty male Wistar rats of SPF grade were randomly divided into a normal group, a model group, a eye-acupuncture point (AA) group and a non-point (NA) group. The D-IBS rat model was established with the combination methods of the chronic stress and binding limbs. The AA group was treated by acupuncture at "low energizer area", "large intestine area", "liver area" and "spleen area", and the NA group by acupuncture at 3 mm apart from the same points area mentioned above, and the normal group and the model group with no intervention. The rate of feces moisture content was detected. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA of aquaporin 8 (AQP 8) in colon. Protein expressions of the vasoactive intestinal peptide (VIP) and AQP 8 in colon were detected by SABC immunohistochemistry method.
RESULTSCompared with normal group, the rate of feces moisture content at the 18th and 25th days, VIP protein in colon mucosa, myenteric nerve plexus and hypo-mucosa nerve plexus increased significantly (all P < 0.01), and AQP 8 mRNA in colon mucosa decreased significantly in model, AA and NA group (P < 0.05, P < 0.01); AQP 8 protein in colon mucosa decreased significantly in model group and NA group (both P < 0.01). Compared with model group, the rate of feces moisture content at the 25th day and VIP protein in colon mucosa decreased significantly (P < 0.01, P < 0.05), and AQP 8 mRNA and protein increased significantly (P < 0.05, P < 0.01) in AA group. Compared with AA group, the rate of feces moisture content at the 25th day and VIP protein in colon mucosa increased significantly (both P < 0.01), and AQP 8 mRNA and protein decreased significantly (both P < 0.01) in NA group.
CONCLUSIONEye-acupuncture has a good therapeutic effect on D-IBS. It is suggested that one of the mechanism is relate to increase AQP 8 in colon tissue and restrain the expression of VIP. Non-point area of eye-acupuncture has no obviously therapeutic effect and so to illustrate the point specificity of eye-acupuncture.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Aquaporins ; genetics ; metabolism ; Colon ; metabolism ; Diarrhea ; genetics ; metabolism ; therapy ; Humans ; Irritable Bowel Syndrome ; genetics ; metabolism ; therapy ; Male ; Rats ; Rats, Wistar ; Vasoactive Intestinal Peptide ; genetics ; metabolism
8.Uptake of exogenous sugars and responses by rice root of young wild-type and ospk1 mutant seedlings.
Yan ZHANG ; Jiahe WU ; Chaozu HE
Chinese Journal of Biotechnology 2012;28(7):847-854
How root system responds to various environmental factors has not yet been fully elucidated. In root, the expression of OsPK1 is mainly in the maturation zone and the root-hair zone of root tip. It is unknown whether the uptake of exogenous sugars by rice seedlings is affected by downregulation of OsPK1. In this study, we used wild-type (WT) and ospk1 rice mutant plants to investigate the uptake of exogenous sugars and the responses of rice seedlings by adding sucrose to 1/2 MS medium or not. The contents of sucrose, glucose, fructose and galactose in leaf blades, sheathes and roots of rice seedlings were measured by GC-MS analysis. The result revealed that direct contact between root and exogenous sugars greatly elevates sugar levels of rice seedlings. And the root length of these seedlings is much longer than that of the seedlings grown in medium omitting exogenous sugars, suggesting that uptake of exogenous sugars by root promotes root elongation. Downregulation of OsPK1 has effects on sugar metabolism and the uptake of exogenous sugars. Semi-quantitative RT-PCR result showed that the expressions of OsPIP2;4, OsPIP2;5 and OsTIP2;1 (three aquaporin genes) in root were greatly upregulated by the direct contact between root and exogenous sugars.
Absorption
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Aquaporins
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genetics
;
metabolism
;
Carbohydrate Metabolism
;
Gene Expression Regulation, Plant
;
Genes, Plant
;
Genetic Variation
;
Oryza
;
genetics
;
metabolism
;
Plant Proteins
;
genetics
;
metabolism
;
Plant Roots
;
metabolism
;
Protein-Serine-Threonine Kinases
;
genetics
;
metabolism
;
Seedlings
;
genetics
;
metabolism
9.Expression of aquaporin 8 and its relationship with melanosis coli.
Jun LIU ; De-An TIAN ; Jun-Ping WANG ; Su-Zhen ZHANG ; Jing FENG ; Zhi-Zhong ZHAO ; Yu-Xia HAO ; Ping LIU
Chinese Medical Journal 2011;124(19):3061-3065
BACKGROUNDThe relationship between melanosis coli (MC) and aquaporin 8 (AQP8) has not yet been elucidated. The aim of this research was to investigate the relationship between the expression of AQP8 and the pathological mechanism of MC.
METHODSExpression of AQP8 was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) in 37 MC colon tissues and 13 control colon tissues. Global gene expression analysis was also used to identify differently expressed genes. Its relationship with MC was analyzed by SPSS 11.5 statistical software.
RESULTSThe positive rate of AQP8 expression detected by immunohistochemistry in the MC group was 24.3% (9/37), significantly lower than the 69.2% (9/13) in the control group (P < 0.05). The relative expression level of AQP8 in MC group was 0.639 ± 0.160, lower than 0.921 ± 0.148 of controls (P < 0.05). Global gene expression analysis showed that AQP8 mRNA expression was downregulated in MC patients.
CONCLUSIONSThe decreased AQP8 expression in MC patients indicates that chronic use of laxatives containing anthraquinone may cause reduced water absorption. The expression of AQP8 may be related to MC.
Adult ; Aged ; Aquaporins ; analysis ; genetics ; Colonic Diseases ; etiology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Male ; Melanosis ; etiology ; Middle Aged
10.Enhanced expression of aquaporin-9 in rat brain edema induced by bacterial lipopolysaccharides.
Huaili, WANG ; Runming, JIN ; Peichao, TIAN ; Zhihong, ZHUO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(2):150-5
To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.
Aquaporins/genetics
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Aquaporins/*metabolism
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Blood-Brain Barrier/metabolism
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Brain/drug effects
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Brain/physiology
;
Brain Edema/chemically induced
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Brain Edema/*metabolism
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Lipopolysaccharides
;
Rats, Sprague-Dawley
;
Water/physiology

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