Congenital renal diabetes insipidus caused by aquaporin 2 gene mutation in siblings: 2 cases report and literature review / 中国综合临床

Objective:To improve clinicians' understanding of congenital nephrogenital diabetes insipidus (CNDI) and to reduce missed and misdiagnosis. Methords 　Based on the literature, the clinical data and gene mutation of 2 patients with CNDI who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Henan University of Science and Technology on July 30, 2020 were analyzed retrospectively. Results:(1) The presentee, 4 years old, had irritable thirst, polydipsia and polyuria for more than 3 years. The sister, 2.5 years old, had irritable thirst, polydipsia and polyuria for more than 2 years. The clinical diagnosis was “CNDI”, and the symptoms improved after treatment with hydrochlorothiazide. (2) The genetic test revealed that the congenital nephrogenic uremia and her sister had a heterozygous mutation of c.170A>C (p.Q57P) and c.211G>A (p.Vl71M) in the aquaporin-2 gene, and the mother carried the AQP2 gene. c.170A>C(p.Q57P) mutation.Conclusion:CNDI is a rare disease. Early diagnosis and treatment can improve the prognosis of patients to the greatest extent, and prenatal diagnosis can guide eugenics.

Elabela alleviates diabetic kidney disease by regulating aquaporin 2 / 中华内分泌代谢杂志

Objective:To assess the renal-protective effect of Elabela (Ela) on diabetic kidney disease (DKD), and explore its potential mechanism.Methods:db/db mice were randomly divided into diabetic group and Ela intervention group, while db/m mice were taken as normal control group. The mice in the Ela intervention group were intraperitoneally injected with Ela-21 5 mg·kg -1·d -1 for 8 weeks. At the end of the experiment, urinary albumin/creatinine ratio (UACR) was measured. The renal pathological changes were observed by HE and PAS staining. The expression of aquaporin 2(AQP2) examined by immunohistochemistry. The level of collage Ⅳ(Col-Ⅳ) and AQP2 in renal tissue was analyzed by Western blot. The human renal tubular epithelial cells (HK-2) were incubated with high glucose medium and further interfered with apelin receptors (APJ)-siRNA. Western blot analysis was used to detect the effect of Ela intervention on Col-Ⅳ and AQP2 expression. Finally, to clarify the possible mechanism of Ela regulating AQP2, the interaction between Ela-induced APJ activation and arginine vasopressin (AVP)-evoked arginine vasopressin receptor 2 (AVPR2) activation was investigated by NanoBit ? technology. Results:(1) Without affecting blood glucose and body weight, Ela intervention significantly reduced the UACR in db/db mice, and attenuate pathological changes of the kidney, as well as expression of Col-Ⅳ and AQP2. (2) Ela treatment could remarkably inhibit the high glucose-induced the expression of Col-Ⅳ and AQP2, which was reversed by interfering with APJ. (3) AVP-induced downstream β-Arrestin-2 signaling transduction via AVPR2 was obviously antagonized by interaction of Ela and APJ, further suggesting that the inhibitory effect of Ela on AQP2 may be related to antagonizing AVP/AVPR2 signaling.Conclusion:Ela exerts renal protection by inhibiting the expression of AQP2 through APJ.

The distribution and function of aquaporin 1 and 2 along the kidney in different species / Distribución y función de la acuaporina 1 y 2 a lo largo del riñón en diferentes especies

SUMMARY: Water metabolism in kidney is critical for organisms living in arid environments. In this study, the kidney structure and the expression of AQP1 and AQP2 in Phrynocephalus vlangalii and Camelus bactrianus were studied. It was found that the Phrynocephalus vlangalii has fewer renal corpuscle but developed kidney tubules, and AQP1 and AQP2 were mainly expressed in the kidney tubules. Camelus bactrianus has a large diameter of glomerulus, thick bulbar membrane, and long and dense urinary tract. AQP1 was highly expressed in the proximal convoluted tubule, proximal straight tubule, and Ansa nephroni (Henle´s loop), and AQP2 was also highly expressed in the collecting tubule and distal convoluted tubule. In the long-term evolutionary adaptation, the morphological structure of animal kidney is consistent with its environment. In addition to structural and functional adaptation, aquaporin also participates in the adaptation to water scarcity environment, and may also play a key role.

RESUMEN: El metabolismo del agua en los riñones es fundamental para los organismos que viven en ambientes áridos. En este estudio, se estudió la estructura renal y la expresión de AQP1 y AQP2 en Phrynocephalus vlangalii y Camelus bactrianus. Se encontró que Phrynocephalus vlangalii tiene menos corpúsculos renales. pero desarrolló túbulos renales, y AQP1 y AQP2 se expresaron principalmente en los túbulos renales. Camelus bactrianus tiene un glomérulo de gran diámetro, una membrana bulbar gruesa y un tracto urinario largo y denso. AQP1 se expresó en gran medida en el túbulo contorneado proximal, el túbulo recto proximal y el Ansa nephroni o asa nefrónica (asa de Henle), y AQP2 también se expresó en gran medida en el túbulo colector y el túbulo contorneado distal. A largo plazo, en la adaptación evolutiva la estructura morfológica del riñón animal es coherente con su entorno. Además de la adaptación estructural y funcional, la acuaporina también es parte de la adaptación al entorno de escasez de agua y puede desempeñar un papel clave.

Clinical characteristics of congenital nephrogenic diabetes insipidus / 中华内科杂志

The purpose of this study was to improve the ability to visualize and diagnose congenital nephrogenic diabetes insipidus (CNDI). The clinical manifestations, laboratory examination findings, imaging features and treatment outcomes of 22 patients with CNDI admitted to the First Affiliated Hospital of Zhengzhou University from May 2013 to May 2020 were retrospectively analyzed. Among the 22 patients with CNDI, 86.4% (19 cases) were male. The age of the 22 patients ranged from 2 months to 47 years old, in which 20 cases were younger than 30 years old and 2 cases were older than 30 years old. The clinical manifestations were polydipsia and polyuria, accompanied with various degrees of fever, defects in growth and development, and increased serum creatinine in some patients. Fifteen patients (68.2%) had different degrees of bilateral kidney and ureteral hydronephrosis, and increased residual urine volume in the bladder. Pituitary magnetic resonance imaging (MRI) enhanced scan showed that the high signal intensity in the posterior pituitary lobe was not detectable in 5 cases (22.7%), and blurred in 6 cases (27.3%). Seven tested patients were all found AVPR2 gene mutation. For patients with suspected CNDI, water-inhibiting vasopressin test and genetic testing should be performed in time so as to confirm diagnosis and treat as early as possible.

Immunohistochemical study of aquaporin 1 and 2 in the hepatobiliary system of Qinghai lizard (Pphrynocephalus vlangalii ) / Estudio inmunohistoquímico de aquaporin 1 y 2 en la sistema hepatobiliar del lagarto de Qinghai ( Phrynocephalus vlangalii )

A serous membrane covering the liver and the hepatic parenchyma, consists of hepatocytes, arteries, veins, hepatic sinusoids and biliary ductuli. There are erythrocytes, thrombocytes, melanin particles and Kupffer cell in the hepatic sinusoids and the blood vessels. The gall bladder wall consists of a mucous layer a muscle layer and a serous layer. The bottom of the epithelium abounds with round or oval secretory. In liver, immunohistochemistry results show that AQP1 have intense reaction in hepatic lobule, Kupffer cells (Macrophagocytus stellatus), hepatocytes, portal tract, blood islands, vein and artery, but almost no reaction of AQP2 was detected. In gallbladder, mucous epithelium, endothelial cells from vein and artery all have strong AQP1 expression, AQP2 showed minor diffused positive reaction in gallbladder, which suggesting that AQP1 may have the main role in the absorption and transportation of fluid in hepatobiliary system of Qinghai Lizard.

Una membrana serosa cubre el hígado y el parénquima hepático el cual está formado por hepatocitos, arterias, venas, sinusoides hepáticos y conductos biliares. Se encuentran eritrocitos, trombocitos, partículas de melanina y células de Kupffer en los sinusoides hepáticos y en los vasos sanguíneos. La pared de la vesícula biliar presenta tres capas: mucosa, muscular y serosa. En el hígado, la inmunohistoquímica mostró que AQP1 tiene una reacción intensa en el lóbulo hepático, células de Kupffer, hepatocitos, tracto portal e islotes sanguíneos. En venas y arterias, no se detectó reacción alguna de AQP2. En la vesícula biliar, el epitelio mucoso, las células endoteliales venosas y arteriales tuvieron una importante expresión de AQP1, sin embargo, AQP2 mostró una reacción positiva difusa menor, lo que sugiere que la AQP1 podría tener una función principal en la absorción y transporte de líquido en el sistema hepatobiliar del Lagarto Qinghai.

Effect of erythropoietin on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats / 中华实用儿科临床杂志

Objective@#To investigate the effect of erythropoietin (EPO) on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats.@*Methods@#Twenty-four SD rats were randomly divided into 3 groups(CUUO-R group, CUUO-R+ EPO group and sham group, with 8 rats in each group). The CUUO-R model was built through unilateral ureteral ligation, after 48 h the obstruction was released.EPO was given to the CUUO-R+ EPO group at the time point of removing obstruction, and then repeated every other day for 1 week, and the same volume of saline was simultaneously given to the CUUO-R rats.The rats in sham group experienced the laparotomy and free dissection of left ureter but not ligation.The kidneys were harvested 7 d after the release of CUUO.The methods of Western blot and immunohistochemistry were used to examine the effects of erythropoietin on the expression of AQP2 and AQP3.@*Results@#The osmotic pressure of CUUO-R+ EPO group was higher than those of CUUO-R group, but lower than that of sham group(P=0.007). The concentration of creatinine and urea in the CUUO-R group[(58.001±2.416) μmol/L and (9.025±1.158) mmol/L]were higher than those of CUUO-R+ EPO group [(57.072±2.286) μmol/L and (1.479±0.043) mmol/L] and sham group [(54.820±1.536) μmol/L and (6.929±0.604) mmol/L]. The differences of the concentration of creatinine and urea between CUUO-R group and sham group were statistically significant(P<0.05). There was no significant difference between CUUO-R+ EPO group and Sham group(P>0.05). The immunohistochemistry showed that the expressions of AQP2 and AQP3 in co-llecting duct in CUUO-R group were significantly weaker than those of in sham group, and the expression of those in CUUO-R+ EPO group were slightly weaker than sham group.These results were further confirmed by Western blot, as the relative quantity of AQP2 and AQP3 were also the lowest in CUUO-R group(AQP2 in 3 groups were 0.974±0.109, 1.923±0.097 and 2.002±0.044, F=392.4, P=0.000; AQP3 in 3 groups were 0.941±0.048, 1.497±0.043 and 1.863±0.043, F=735.8, P=0.000).@*Conclusions@#EPO treatment is beneficial for the recovery expre-ssion of AQP2 and AQP3 as well as renal function at the early period after the release of ureteral obstruction in young rats.

Comparison of Dryness Effect Between Atractylodes lancea and A. chinensis / 中国实验方剂学杂志

Objective:To investigate the dryness effect of Atractylodes lancea and A. chinensis. Method:Sixty normal and healthy SD rats were randomly divided into 6 groups(10 in each group), including normal saline group, soybean oil group, low-dose(46.25 mg·kg-1·d-1) group and high-dose(500 mg·kg-1·d-1) group of A. lancea, low-dose(46.25 mg·kg-1·d-1) group and high-dose(500 mg·kg-1·d-1) group of A. chinensis, the dosing volume was 0.01 mL·g-1, and the drug was administered orally for 21 days. Taking average daily water intake, submandibular gland tissue, urine volume and expression of aquaporin 2(AQP2) in the kidney, and whole blood viscosity as the evaluation indexes, the dryness effect of long-term administration of equal doses of volatile oil from A. lancea and volatile oil from A. chinensis on rats was observed. Result:Compared with the soybean oil group, long-term administration of high doses of volatile oil from A. lancea and volatile oil from A. chinensis could significantly increase average daily water intake, urine volume and whole blood viscosity; decrease the expression of AQP2, and atrophy the acini of submandibular gland, but there was no significant difference between the two groups. Effects of volatile oil from A. lancea and A. chinensis with low dose on dryness of rats were not significant. Conclusion:There is no significant difference between the dryness effect of volatile oil from A. lancea and A. chinensis in the same dose. It is proved that the rationality of A. lancea and A. chinensis are universal in clinical practice, and this study provides experimental basis for rational use of Atractylodis Rhizoma.

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Eendolymphatic Hydrops / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of electroacupuncture (EA) on endolymphatic hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2) pathway in guinea pigs.@*METHODS@#EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP) levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the cochlea were compared among groups.@*RESULTS@#EA significantly reduced cochlear hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVPinduced up-regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA (P=0.004) in the cochlea.@*CONCLUSIONS@#The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.

New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.

Effect of erythropoietin on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats / 中华实用儿科临床杂志

Objective To investigate the effect of erythropoietin (EPO) on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats.Methods Twenty-four SD rats were randomly divided into 3 groups(CUUO-R group,CUUO-R + EPO group and sham group,with 8 rats in each group).The CUUO-R model was built through unilateral ureteral ligation,after 48 h the obstruction was released.EPO was given to the CUUO-R + EPO group at the time point of removing obstruction,and then repeated every other day for 1 week,and the same volume of saline was simultaneously given to the CUUO-R rats.The rats in sham group experienced the laparotomy and free dissection of left ureter but not ligation.The kidneys were harvested 7 d after the release of CUUO.The methods of Western blot and immunohistochemistry were used to examine the effects of erythropoietin on the expression of AQP2 and AQP3.Results The osmotic pressure of CUUO-R + EPO group was higher than those of CUUO-R group,but lower than that of sham group (P =0.007).The concentration of creatinine and urea in the CUUO-R group [(58.001 ± 2.416) μmol/L and (9.025 ± 1.158) mmol/L] were higher than those of CUUO-R + EPO group [(57.072 ± 2.286) μmol/L and (1.479 ± 0.043) mmol/L] and sham group [(54.820 ± 1.536) μmol/L and (6.929-±0.604) mmol/L].The differences of the concentration of creatinine and urea between CUUO-R group and sham group were statistically significant (P ＜ 0.05).There was no significant difference between CUUO-R + EPO group and Sham group(P ＞ 0.05).The immunohistochemistry showed that the expressions of AQP2 and AQP3 in collecting duct in CUUO-R group were significantly weaker than those of in sham group,and the expression of those in CUUO-R + EPO group were slightly weaker than sham group.These results were further confirmed by Western blot,as the relative quantity of AQP2 and AQP3 were also the lowest in CUUO-R group (AQP2 in 3 groups were 0.974 ± 0.109,1.923 ± 0.097 and 2.002 ± 0.044,F =392.4,P =0.000;AQP3 in 3 groups were 0.941 ± 0.048,1.497 ± 0.043 and 1.863 ± 0.043,F =735.8,P =0.000).Conclusions EPO treatment is beneficial for the recovery expression of AQP2 and AQP3 as well as renal function at the early period after the release of ureteral obstruction in young rats.

Significance and expression of aquaporin-2 in fetus kidney and amniotic fluid at different stages of the pregnancy / 中华实用儿科临床杂志

Objective To explore the expression of aquaporin-2 (AQP-2) in human fetus kidney and amniotic fluid at different stages of pregnancy.Methods Twenty-two cases of aborted fetuses' kidneys were collected.They were divided into 3 groups according to the pregnancy age:8 cases in 17-23 + 6 weeks,8 cases in 24-31 +6 weeks,and 6 cases in 32-38 +6 weeks.Western blot was used to examine the expression of AQP-2 in the kidney.Twenty-four cases of the amniotic fluid were collected,and they were divided into 3 groups according to the pregnancy age:10 cases in 17-23 +6 weeks,6 cases in 24-31 +6 weeks,and 8 cases in 32-38 +6 weeks.Eight cases of healthy adult morning urine were collected as positive controls.The AQP-2 protein in the amniotic fluid was detected with the method of enzyme-linked immunosorbent assay (ELISA) and the osmotic pressure of amniotic fluid at different stages of the pregnancy was measured with the freezing point osmometer.Results The expression of AQP-2 was increased with the extending of pregnancy age,and the AQP-2 expressions in fetus kidney of 17-23 +6 weeks,24-31 + 6 weeks and 32-38 +6 weeks were 0.986 ± 0.335,1.566 ± 0.272,and 2.080 ± 0.246,respectively,and the difference was significant (P ＜ 0.05).The AQP-2 detected from amniotic fluid was positively correlated with the result of AQP-2 in the kidney(r =0.985,P ＜ 0.05),and the AQP-2 expression also increased with the extending of pregnancy age:17-23 +6 weeks,24-31 +6 weeks,32-38 +6 weeks and adult urine was (30.253 ±5.843) mg/L,(35.103 ±7.271) mg/L,and (42.580 ± 1.230) mg/L and (46.493 ± 0.450) mg/L,respectively.The osmolality of the amniotic fluid of 17-23 +6 weeks,24-31 +6 weeks,32-38 +6 weeks was (272.600 ± 4.827) mmol/L,(252.00 ± 15.360) mmol/L,and (261.750 ±5.560) mmol/L,respectively,and the difference was significant(P ＜0.05).Conclusions The AQP-2 expression in human fetus kidneys has good correlation with amniotic fluid,which indicates that the level of AQP-2 of the amniotic fluid may reflect the expression of AQP-2 in the fetus kidney.

Expression of AQP1 and AQP2 in renal tissue of congenital hydronephrosis and its correlation with glomerular filtration rate / 国际检验医学杂志

Objective To investigate the expression of aquaporin 1(AQP1)and AQP2 in renal tissue of congenital hydronephrosis and its correlation with glomerular filtration rate(GFR).Methods Renal tissue specimens in 43 children cases of pathologically confirmed congenital hydronephrosis and normal kidney tissue specimens in 16 cases of operation were selected as the case group and healthy control group,the Western-blot and reverse transcription polymerase chain reaction were adopted to detect the expression levels of AQP 1, AQP2 protein and gene in the two groups,and its relationship with GFR was analyzed.Results The expres-sion levels of kidney tissue AQP1,AQP2 protein and gene in the case group were significantly lower than those in the healthy control group,the difference was statistically significant(P<0.05);the urine osmolality and GFR level in the case group were significantly lower than those in the healthy control group,while BUN and Scr levels in the case group were higher than those in the healthy control group,the difference was statis-tically significant(P< 0.05);the GFR level in the case group was positively correlated with AQP 1,AQP2 protein and gene expression levels(P<0.01).Conclusion The expression of AQP1 and AQP2 in renal tissue of congenital hydronephrosis is dow n-regulated,moreover is closely related to the disease severity degree.

Effect of Zhenwu Tang on regulating of "AVP-V2R-AQP2" pathway in NRK-52E cells / 中国中药杂志

This study was aimed to investigate the effect and mechanism of Zhenwu Tang on AVP-V2R-AQP2 pathway in NRK-52E cells . Forty eight male SD rats were randomly divided into eight groups with 6 animals in each group. Distilled water or 22.68 g·kg⁻¹·d⁻¹ Zhenwu Tang(calculated by raw drug dosage meter) was given by gavage. Blood samples were collected by cardiac puncture， and the medicated serum was centrifuged from the blood by 3 000 r·min⁻¹. NRK-52E cells were treated with different medicated serum or dDAVP. The condition of cell proliferation was detected by RTCA. The distribution of V2R and AQP2 in cells were detected by immunofluorescence. The expression of V2R， PKA and AQP2 were detected by Western blot and AQP2 mRNA level was detected by real-time PCR. Results showed that the level of AQP2 mRNA(<0.01) and protein expression of V2R， PKA and AQP2(<0.05， <0.01， <0.05) of Z7d group which was treated with Zhenwu Tang medicated serum for 24 h were significantly higher than that of normal rat serum group. And the expression level of V2R， p-AQP2 and AQP2(<0.01， <0.05， <0.01) of Z7d+dDAVP group were significantly increased comparing to normal rat serum group. The results indicate that the applying of Zhenwu Tang medicated serum could increase the expression level of V2R， PKA and AQP2 which exist in AVP-V2R-AQP2 pathway in NRK-52E， and there is synergistic effect between Zhenwu Tang medicated serum and dDAVP. So the pathway of AVP-V2R-AQP2 may be one of the mechanism for which Zhenwu Tang regulate balance of water transportation.

Influence of infusion of mesenchymal stem cells by different routes on the expression of AQP1 and AQP2 in rats with adriamycin-induced nephropathy / 介入放射学杂志

Objective To evaluate the therapeutic effect of bone marrow mesenchymal stem cell (MSC) infusion transplantation via renal artery and via caudal vein in treating chronic kidney disease (CKD) in rats,and to compare the expressions of aquaporin1 (AQP1) and aquaporin2 (AQP2) between the two transplantation routes.Methods A total of 50 male SD rats were selected for this experiment.Two experimental rats were used to make preparation of bone marrow MSC.CKD model was established with infusion of adriamycin via caudal vein in 36 rats.The 36 CKD models were randomly divided into adriamycininduced renal failure model control group (A-C group,n=12),MSC transplantation through the right renal artery group (M-A group,n=12) and MSC transplantation through the caudal vein group (M-V group,n=12).The remaining 12 male SD rats were used as the blank control group (N group).One week after the last bone marrow MSC transplantation,the 24 h urine volume,24 h urinary protein content,serum sodium content and serum albumin level were measured,and AQP1 and AQP2 expressions in the kidney tissue were determined by immunohistochemistry.Results Compared with A-C group,the serum albumin level and 24h urine volume in both M-V group and M-A group were significantly increased (P＜0.05),while 24h urinary protein content and serum sodium content were remarkably decreased (P＜0.05).The 24h urinary protein content in the M-A group was obviously lower than that in the M-V group (P＜0.05).The AQP1 and AQP2 expressions in the kidney tissue in both M-V group and M-A group were strikingly lower than those in the A-C group (P＜ 0.05),but no statistically significant differences in AQP1 and AQP2 expressions existed between the M-V group and the M-A group (P＞0.05).Conclusion MSC transplantation can increase serum albumin,and lower urinary protein,serum sodium and the expressions of AQP1 and AQP2 in renal parenchymal cells,which has the effect on repairing renal injury of adriamycin-induced CKD rats.For a given period of time,the clinical curative effect of MSC transplantation via renal artery is better than that of MSC transplantation via peripheral vein,but the difference in curative effect between the two MSC transplantation pathways has no obvious correlation with AQP1 and AQP2 expressions.

Immunohistochemical study of aquaporin 1 and 2 in the reproductive tract of the bactrian camel (Camelus bactrianus) / Estudio inmunohistoquímico de acuaporina 1 y 2 en el tracto reproductivo del camello bactriano (Camelus bactrianus)

Spermatogenesis is associated with considerable fluid secretion or absorption in the male reproductive tract. Aquaporins (AQPs) are membrane protein channels that allow the rapid movement of water through epithelium. In the present study, immunohistochemistry was utilized to localize the expression of AQP 1, AQP2 in the testis and prostate of adult bactrian camel (Camelus bactrianus). Results show that AQP1 have intense reaction in rete testis, efferent ducts, vessels, seminiferous duct and in the prostate, AQP2 was found minor expression in the rete testis, vessels and prostate, which suggesting that AQP1 may have the main role in the absorption of the large amount of testicular fluid in male camel reproductive tract. Investigations of AQPs biology in camel could be relevant with technologies for assisted procreation in animal husbandry and aquaculture.

La espermatogénesis se asocia con la secreción de una cantidad considerable de líquido o absorción en el tracto reproductor masculino. Las acuaporinas (ACPs) son canales de proteínas de membrana que permiten el movimiento rápido de agua a través del epitelio. En el presente estudio, se utilizó inmunohistoquímica para localizar la expresión de ACP 1, ACP2 en el testículo y la próstata del camello bactriano adulto (Camelus bactrianus). Los resultados muestran que ACP1 tiene una reacción intensa en la rete testis, conductos eferentes, vasos, conductos seminíferos y en la próstata. La expresión ACP2, de menor importancia, se observó en la rete testis, vasos y próstata, lo que sugiere que ACP1 puede tener el papel principal en la absorción de gran cantidad de líquido testicular en el tracto reproductivo masculino del camello. Las investigaciones de la biología del ACP en camello podrían ser relevantes para las tecnologías de reproducción asistida de la ganadería y la acuicultura.

Effect of Diet and Water Intake on Aquaporin 2 Function

Appropriate control of diet and water intake is important for maintaining normal blood pressure, fluid and electrolyte homeostasis in the body. It is relatively understood that the amount of sodium and potassium intake directly affects blood pressure and regulates ion transporters; Na and K channel functions in the kidney. However, little is known about whether diet and water intake regulates Aquaporin (AQP) function. AQPs, a family of aquaporin proteins with different types being expressed in different tissues, are important for water absorption by the cell. Water reabsorption is a passive process driven by osmotic gradient and water permeability is critical for this process. In most of the nephron, however, water reabsorption is unregulated and coupled to solute reabsorption, such as AQP1 mediated water absorption in the proximal tubule. AQP2 is the only water channel founded so far that can be regulated by hormones in the kidney. AQP2 expressed in the apical membrane of the principal cells in the collecting tubule can be regulated by vasopressin (antidiuretic hormone) controlling the final volume of urine excretion. When vasopressin binds to its receptor on the collecting duct cells, it stimulates the translocation of AQP2 to the membrane, leading to increased water absorption via this AQP2 water channel. However, some studies also indicated that the AQP2 is also been regulated by vasopressin independent mechanism. This review is focused on the regulation of AQP2 by diet and the amount of water intake on salt and water homeostasis.

Urine AQP2 change in patients with asthma controlled to different clinical levels and its relationship with inflammatory factors / 第二军医大学学报

Objective To compare the urine aquaporin 2 (AQP2) levels between asthmatic patients and healthy participants, explore the AQP2 levels in patients with asthma of different clinical control levels and its relationship with inflammatory factors. Methods Urine AQP2 levels were examined by ELISA in 60 patients with asthma and 21 healthy participants; plasma interleukin (IL)-4, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ levels were determined by by CBA method. Results The levels of urine AQP2 in clinical uncontrolled asthma group (ACT below 19) and partially controlled asthma group (ACT 20~24) were significantly higher than that in the healthy control group(P<0.01), and the level in the uncontrolled group was (174.28±40.81)pg/mL. The plasma IL-4 level in uncontrolled group was (1.10±0.25)pg/mL, which was significantly higher than those in the other two groups (P<0.01). The plasma IL-6 level in uncontrolled asthma group was the highest but showing no significant difference when compared with the other two groups(P=0.058). The TNF-α level in asthma patients was significantly higher than that in healthy controls(P<0.05). Urine AQP2 was found significantly correlated with plasma IL-4 and IL-6 levels(P=0.049,P=0.010); plasma IL-4 level was significantly correlated with IFN-γ level(P=0.019); IL-6 was significantly correlated with TNF-α level(P=0.010); and IL-10 was significantly correlated with IFN-γ levle(P=0.005). Conclusion Urine AQP2 level of asthma patients is increased, and it is significantly correlated with plasma levels of inflammatory factors IL-4 and IL-6. The role of AQP2 in the pathogenesis of bronchial asthma is worth further studying.

Expression of leptin receptor and aquaporin 2 in kidneys of obesity-related hyperten-sive rats / 军事医学

Objective To observe the expression of leptin(Lep) receptor (LepR) and aquaporin 2 (AQP2) in the kidneys of obesity-related hypertensive rats ( OHR ) and to explore the mechanism of Lep resistance and water metabolic disorders in them.Methods OHR( model group) were induced by high-fat diet.Normal Wistar rats were chosen as normal control and hypertensive rats(SHR) as positive control.The serum level of triglycerides(TG), total cholesterol(TC), Lep, vasopressin ( AVP ) , angiotensinⅡ( AngⅡ) and β2-microglobulin (β2-MG ) was measured by enzyme linked immunosorbent assays ( ELISA) and renal morphology was observed by HE staining.The density of LepR and AngⅡtype 1( AT1) in the kidney was observed by immunohistochemistry.mRNA And protein expression of LepR and AQP2 in the kidney was assayed by real-time polymerase chain reaction and Western blotting.Results Compared with normal rats,the TG, TC, Lep, AVP, AngⅡand β2-MG of the model group were significantly increased (P<0.05), and protein and mRNA expression of LepR and AQP2 in the kidney were up-regulated (P<0.05).Compared with SHR group, TG, TC and Lep in serum of the model group were significantly increased (P<0.05).The concentrations of AVP,β2-MG and Lep was linearly related(R2 =0.87,R2 =0.95).Conclusion Water metabolic disorder and Lep resistance may be involved in the kidney injury of OHR, which may be one of the important pathogeneses of obesity-related hypertension.

Experimental investigates on changes of expression of Aquaporin2 (AQP2) in renal of rats with obstructive jaundice / 中国免疫学杂志

Objective:To investigate the change of expression of AQP 2 in renal of obstructive jaundice rats , and the relationship between AQP 2 and the changing of Cr and BUN.Methods: Legated the common bile duct of rats to form the obstructive jaundice group.Scarified the rats on the 3th,5th,7th,10th,14th day,took blood samples and the kidney of the rats.Test direct bilirubin BUN and Cr in serum,the renal histopathological changes were observed by optical microscopy .The expression of AQP2 in renal of rats was tested by using radio immunological method.Results: Light microscopic examination of kidney showed that swelling epithelium arranged irregularly in 3rd day ,bleb in the 5th day.The expression of AQP2 in renal of rats with obstructive jaundice were greatly less than sham operation.Mesenchyma inflammatory cells infiltrate in 7th day.Local epithelial necrosis and lots of inflammatory cells infiltrate in the mesenchyma in 10th day and 14th day.The expression of AQP2 in renal collective tubule was decreased on the 5th day compared with sham operation ,and the decrease was more as time gone by.The renal function injury can be confirmed though the renal collective tubule change.Cr and BUN in serum began to increase on the 10th day and 14th day.Conclusion: Decrease of AQP2 is earlier than the increase of Cr and BUN ,and it can be the early sign of renal function injury.

Diabetes insípida nefrogénica / Nephrogenic diabetes insipidus

La hormona antidiurética arginina vasopresina (AVP) es liberada de la hipófisis, y regula la reabsorción de agua en las células principales del túbulo colector renal. La unión de la AVP al receptor tipo 2 de la AVP en la membrana basolateral induce la translocación de los canales acuosos de la acuaporina-2 hacia la membrana apical de las células principales de los túbulos colectores, induciendo la permeabilidad al agua de la membrana. Lo anterior da como resultado la reabsorción de agua en el túbulo colector de la nefrona, bajo la influencia de un gradiente osmótico. La diabetes insípida nefrogénica es causada por la resistencia parcial o total al efecto de la AVP. La diabetes insípida nefrogénica congénita es una alteración asociada con mutaciones en los genes AVPR2 o AQP2, ocasionando la incapacidad del paciente para concentrar la orina. La diabetes insípida nefrogénica adquirida o secundaria puede ser causada por desbalances electrolíticos (hipercalcemia, hipokalemia), enfermedades renales o extrarrenales y fármacos (toxicidad por litio). En este artículo se revisan las causas, manifestaciones clínicas, diagnóstico y tratamiento de los pacientes con diabetes insípida nefrogénica. También, con base en la comprensión de los mecanismos íntimos de la alteración, se exploran nuevas estrategias terapéuticas.

The anti-diuretic hormone arginine-vasopressin (AVP) is released from the pituitary and regulates water reabsorption in the principal cells of the kidney collecting duct. Binding of AVP to the arginine-vasopressin receptor type-2 in the basolateral membrane leads to translocation of aquaporin-2 water channels to the apical membrane of the principal cells of the collecting duct, inducing water permeability of the membrane. This results in water reabsorption in the collecting duct of the nephron following an osmotic gradient. Nephrogenic diabetes insipidus is caused by partial or complete renal resistance to the effects of AVP. Congenital nephrogenic diabetes insipidus is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their urine. Acquired nephrogenic diabetes insipidus can be caused by electrolyte imbalances (e.g., hypercalcemia, hypokalemia), renal/extra-renal diseases and drugs (e.g., lithium toxicity). This article reviews the causes, clinical manifestations, diagnosis and treatment of patients with nephrogenic diabetes insipidus. Based on more in-depth mechanistic understanding, new therapeutic strategies are current being explored.