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  • 4区Q3影响因子: 2
    1. Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease.
    作者:Bourgeois Soline , Bettoni Carla , Baron Stéphanie , Wagner Carsten A
    期刊:Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
    日期:2018-05-25
    DOI :10.1159/000490186
    BACKGROUND/AIMS:Homozygous mutations or deletion of the ATP6V1B1 gene encoding for the B1 subunit of the vacuolar H+-ATPase leads to distal renal tubular acidosis in man and mice. In humans, heterozygous carriers of B1 mutations can develop incomplete dRTA with nephroclacinosis. Here, we investigated whether Atp6v1b1+/- mice also develop acid-base disturbances during an HCl acid load. METHODS:We subjected Atp6v1b1+/+, Atp6v1b1+/-, Atp6v1b1-/- to an HCl-load for 7 days and investigated acid-base status, kidney function, and expression of renal acid-base transport proteins. RESULTS:Atp6v1b1-/- mice had more alkaline urine and low ammoniuria, whereas Atp6v1b1+/- mice showed no difference in their urine parameters but higher blood chloride and lower blood pCO2 compared to controls. Subcellular localization of a4 and B2 subunits of H+-ATPase were unchanged within the 3 genotypes and Atp6v1b1+/+ and Atp6v1b1+/- mice exhibited a similar luminal localization of B1 subunit in intercalated cells. However, B1, B2 and a4 expression were decreased in renal membrane fractions from Atp6v1b1+/- mice compared to Atp6v1b1+/+ while B2 and a4 were unchanged and B1 protein was reduced in Atp6v1b+-/- kidneys. Compensatory mechanisms of B1 ablation were found only in the collecting duct with a down-regulation of pendrin in Atp6v1b1-/- mice. CONCLUSIONS:In conclusion, 1) Atp6v1b1+/- mice developed a mild incomplete dRTA. dRTA is partly compensated by respiration. 2) Compensatory mechanisms for the absence of B1 take place only in the collecting duct of Atp6v1b1-/- kidneys.
  • 1区Q1影响因子: 12.6
    2. Kidney tubular transcription co-activator, Yes-associated protein 1 (YAP), controls the expression of collecting duct aquaporins and water homeostasis.
    期刊:Kidney international
    日期:2022-11-01
    DOI :10.1016/j.kint.2022.10.007
    Final urine volume and concentration are defined by water reabsorption through the water channel proteins aquaporin (AQP)-2, -3 and -4 in the collecting duct. However, the transcriptional regulation of these AQPs is not well understood. The Hippo/Yes-associated protein 1 (YAP) pathway plays an important role in organ size control and tissue homeostasis. When the Hippo pathway including the Mst1/Mst2 kinases is inhibited, YAP is activated and functions as a transcription co-activator. Our previous work revealed a pathological role of tubular YAP activation in chronic kidney disease, but the physiological role of YAP in the kidney remains to be established. Here, we found that tubule-specific Yap knockout mice showed increased urine output and decreased urinary osmolality. Decreases in Aqp2, -3 and -4 mRNA and protein abundance in the kidney were evident in Yap knockout mice. Analysis of Mst1/Mst2 double knockout and Mst1/Mst2/Yap triple knockout mice showed that expression of Aqp2 and Aqp4 but not Aqp3 was dependent on YAP. Furthermore, YAP was recruited to the promoters of the Aqp2 and Aqp4 genes and stimulated their transcription. Interestingly, YAP was found to interact with transcription factors GATA2, GATA3 and NFATc1. These three factors promoted Aqp2 transcription in a YAP dependent manner in collecting duct cells. These three factors also promoted Aqp4 transcription whereas only GATA2 and GATA3 enhanced Aqp3 transcription. Thus, our results suggest that YAP promotes Aqp2 and Aqp4 transcription, interacts with GATA2, GATA3 and NFATc1 to control Aqp2 expression, while Aqp-2, -3 and -4 exploit overlapping mechanisms for their baseline transcriptional regulation.
  • 2区Q1影响因子: 6.6
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    3. Multi-Effects of Acute Salinity Stress on Osmoregulation, Physiological Metabolism, Antioxidant Capacity, Immunity, and Apoptosis in .
    期刊:Antioxidants (Basel, Switzerland)
    日期:2023-10-07
    DOI :10.3390/antiox12101836
    Salinity stress can trigger a series of physiological changes. However, the mechanism underlying the response to acute salinity stress in remains poorly understood. In this study, osmoregulation, physiological metabolism, antioxidant capacity, and apoptosis were examined over 96 h of acute salinity stress. Hemolymph osmolality increased with increasing salinity. After 48 h of salinity exposure, the glucose, triglycerides, total protein, and total cholesterol contents in two salinity stress groups (13 and 26‱ salinity) were significantly lower than those in the 0‱ salinity group. The highest levels of these parameters were detected at 6 h; however, superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) were the lowest at 96 h in the 13‱ salinity group. The activity of immunity-related enzyme alkaline phosphatase (AKP) showed a decreasing trend with increasing salinity and remained at a low level in the 26‱ salinity group throughout the experiment. No significant differences were observed in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or lysozyme (LZM) among the three treatments at 96 h. After 96 h of salinity treatments, the gill filament diameter significantly decreased, and a more pronounced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive signal was detected in the 13‱ and 26‱ groups compared to that in the 0‱ group. Expression levels of apoptosis-related genes, including Cysteine-aspartic acid protease 3 (), Cysteine-aspartic acid protease 8 (), Cytochrome c (), tumor suppressor gene (), Nuclear factor kappa-B (), and B cell lymphoma 2 ovarian killer () were significantly higher in the 26‱ salinity group than in the other groups at 24 h, but lower than those in the 0‱ salinity group at 96 h. and levels exhibited a significantly positive relationship with MDA, AST, and LZM activity during salinity stress. In the 13‱ salinity group, expression was significantly correlated with SOD, T-AOC, AKP, acid phosphatase, and LZM activity, whereas in the 26‱ group, the AST content was positively correlated with , , and expression. A significant negative relationship was observed between expression and catalase (CAT) activity. These findings provide insight into the mechanisms underlying the response to acute salinity stress and will contribute to improving aquaculture and management practices.
  • 影响因子: 3.4
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    4. Na delivery and ENaC mediate flow regulation of collecting duct endothelin-1 production.
    期刊:American journal of physiology. Renal physiology
    日期:2012-02-22
    DOI :10.1152/ajprenal.00034.2012
    Collecting duct (CD) endothelin-1 (ET-1) is an important autocrine inhibitor of Na and water transport. CD ET-1 production is stimulated by extracellular fluid volume expansion and tubule fluid flow, suggesting a mechanism coupling CD Na delivery and ET-1 synthesis. A mouse cortical CD cell line, mpkCCDc14, was subjected to static or flow conditions for 2 h at 2 dyn/cm(2), followed by determination of ET-1 mRNA content. Flow with 300 mosmol/l NaCl increased ET-1 mRNA to 65% above that observed under static conditions. Increasing perfusate osmolarity to 450 mosmol/l with NaCl or Na acetate increased ET-1 mRNA to ∼184% compared with no flow, which was not observed when osmolarity was increased using mannitol or urea. Reducing Na concentration to 150 mosmol/l while maintaining total osmolarity at 300 mosmol/l with urea or mannitol decreased the flow response. Inhibition of epithelial Na channel (ENaC) with amiloride or benzamil abolished the flow response, suggesting involvement of ENaC in flow-regulated ET-1 synthesis. Aldosterone almost doubled the flow response. Since Ca(2+) enhances CD ET-1 production, the involvement of plasma membrane and mitochondrial Na/Ca(2+) exchangers (NCX) was assessed. SEA0400 and KB-R7943, plasma membrane NCX inhibitors, did not affect the flow response. However, CGP37157, a mitochondrial NCX inhibitor, abolished the response. In summary, the current study indicates that increased Na delivery, leading to ENaC-mediated Na entry and mitochondrial NCX activity, is involved in flow-stimulated CD ET-1 synthesis. This constitutes the first report of either ENaC or mitochondrial NCX regulation of an autocrine factor in any biologic system.
  • 1区Q1影响因子: 19.1
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    5. Regulation of Vascular and Renal Function by Metabolite Receptors.
    作者:Peti-Peterdi János , Kishore Bellamkonda K , Pluznick Jennifer L
    期刊:Annual review of physiology
    日期:2015-11-19
    DOI :10.1146/annurev-physiol-021115-105403
    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis-from salt and water balance to metabolism-by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families-(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and
  • 1区Q1影响因子: 5.3
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    6. Renal Dopamine Oxidation and Inflammation in High Salt Fed Rats.
    作者:Banday Anees A , Lokhandwala Mustafa F
    期刊:Journal of the American Heart Association
    日期:2019-12-27
    DOI :10.1161/JAHA.119.014977
    Background Oxidative stress and high salt intake could be independent or intertwined risk factors in the origin of hypertension. Kidneys are the major organ to regulate sodium homeostasis and blood pressure and the renal dopamine system plays a pivotal role in sodium regulation during sodium replete conditions. Oxidative stress has been implicated in renal dopamine dysfunction and development of hypertension, especially in salt-sensitive animal models. Here we show the nexus between high salt intake and oxidative stress causing renal tubular dopamine oxidation, which leads to mitochondrial and lysosomal dysfunction and subsequently causes renal inflammation and hypertension. Methods and Results Male Sprague Dawley rats were divided into the following groups, vehicle (V)-tap water, high salt (HS)-1% NaCl, L-buthionine-sulfoximine (BSO), a prooxidant, and HS plus BSO without and with antioxidant resveratrol (R) for 6 weeks. Oxidative stress was significantly higher in BSO and HS+BSO-treated rat compared with vehicle; however, blood pressure was markedly higher in the HS+BSO group whereas an increase in blood pressure in the BSO group was modest. HS+BSO-treated rats had significant renal dopamine oxidation, lysosomal and mitochondrial dysfunction, and increased renal inflammation; however, HS alone had no impact on organelle function or inflammation. Resveratrol prevented oxidative stress, dopamine oxidation, organelle dysfunction, inflammation, and hypertension in BSO and HS+BSO rats. Conclusions These data suggest that dopamine oxidation, especially during increased sodium intake and oxidative milieu, leads to lysosomal and mitochondrial dysfunction and renal inflammation with subsequent increase in blood pressure. Resveratrol, while preventing oxidative stress, protects renal function and mitigates hypertension.
  • 3区Q1影响因子: 4.6
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    7. Sugar, salt, immunity and the cause of primary hypertension.
    期刊:Clinical kidney journal
    日期:2023-03-23
    DOI :10.1093/ckj/sfad058
    Despite its discovery more than 150 years ago, the cause of primary hypertension remains unknown. Most studies suggest that hypertension involves genetic, congenital or acquired risk factors that result in a relative inability of the kidney to excrete salt (sodium chloride) in the kidneys. Here we review recent studies that suggest there may be two phases, with an initial phase driven by renal vasoconstriction that causes low-grade ischemia to the kidney, followed by the infiltration of immune cells that leads to a local autoimmune reaction that maintains the renal vasoconstriction. Evidence suggests that multiple mechanisms could trigger the initial renal vasoconstriction, but one way may involve fructose that is provided in the diet (such as from table sugar or high fructose corn syrup) or produced endogenously. The fructose metabolism increases intracellular uric acid, which recruits NADPH oxidase to the mitochondria while inhibiting AMP-activated protein kinase. A drop in intracellular ATP level occurs, triggering a survival response. Leptin levels rise, triggering activation of the sympathetic central nervous system, while vasopressin levels rise, causing vasoconstriction in its own right and stimulating aldosterone production via the vasopressin 1b receptor. Low-grade renal injury and autoimmune-mediated inflammation occur. High-salt diets can amplify this process by raising osmolality and triggering more fructose production. Thus, primary hypertension may result from the overactivation of a survival response triggered by fructose metabolism. Restricting salt and sugar and hydrating with ample water may be helpful in the prevention of primary hypertension.
  • 1区Q1影响因子: 12.6
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    8. Self-maintaining macrophages within the kidney contribute to salt and water balance by modulating kidney sympathetic nerve activity.
    期刊:Kidney international
    日期:2023-05-22
    DOI :10.1016/j.kint.2023.04.023
    The kidney is critical in controlling salt and water balance, with the interstitium involved with a variety of components including immune cells in steady state. However, the roles of resident immune cells in kidney physiology are largely unknown. To help unravel some of these unknowns, we employed cell fate mapping, and identified a population of embryo-derived self-maintaining macrophages (SM-MØ) that were independent of the bone marrow in adult mouse kidneys. This kidney-specific SM-MØ population was distinctive from the kidney monocyte-derived macrophages in transcriptome and in their distribution. Specifically, the SM-MØ highly expressed nerve-associated genes; high-resolution confocal microscopy revealed that the SM-MØ in the cortex were in close association with sympathetic nerves and there was a dynamical interaction between macrophages and sympathetic nerves when live kidney sections were monitored. Kidney-specific depletion of the SM-MØ resulted in reduced sympathetic distribution and tone, leading to reduced renin secretion, increased glomerular filtration rate and solute diuresis, which caused salt decompensation and significant weight loss under a low-salt diet challenge. Supplementation of L-3,4-dihydroxyphenylserine which is converted to norepinephrine in vivo rescued the phenotype of SM-MØ-depleted mice. Thus, our findings provide insights in kidney macrophage heterogeneity and address a non-canonical role of macrophages in kidney physiology. In contrast to the well-appreciated way of central regulation, local regulation of sympathetic nerve distribution and activities in the kidney was uncovered.
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