Vascular Type 1 Angiotensin Receptors Control Blood Pressure by Augmenting Peripheral Vascular Resistance in Female Mice.
Abstract Angiotensin (Ang) II is a major mediator of hypertension pathogenesis. In addition, there are well-documented differences in expression of the renin angiotensin system (RAS) components and Ang II responses between males and females, which may explain sex differences in blood pressure (BP) and hypertension epidemiology. We have previously shown that type 1A Angiotensin (AT1A) receptors in vascular smooth muscle cells (VSMCs) play a critical role in BP regulation and hypertension pathogenesis, but these studies were carried out in male mice. Therefore, the major goal of these studies is to examine the impac...
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Wolf E, Diaz EJ, Hollis A, Hoang TA, Azad HA, Bendt KM, Griffiths RC, Sparks MA Tags: Am J Physiol Renal Physiol Source Type: research

Dual gain and loss of cullin 3 function mediates familial hyperkalemic hypertension.
In conclusion, deletion of exon 9 from Cul3 generates a protein that is itself ubiquitin ligase-defective, but also capable of enhanced autophagocytic KLHL3 degradation, thereby exerting dominant-negative effects on the WT-allele. PMID: 29897280 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Cornelius RJ, Zhang C, Erspamer KJ, Agbor LN, Sigmund CD, Singer JD, Yang CL, Ellison DH Tags: Am J Physiol Renal Physiol Source Type: research

Autophagy activation in circulating proangiogenic cells (PACs) aggravates AKI in type I diabetes mellitus.
CONCLUSION: Pharmacological autophagy activation may most likely not serve as effective strategy for improving PAC competence in diabetic AKI in general. On the contrary, several outcome parameters (excretory function, fibrosis, EndoMT) may even be worsened. PMID: 29897281 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Schwarze K, Kribben A, Ritter O, Müller GA, Patschan D Tags: Am J Physiol Renal Physiol Source Type: research

Divergent effects of AKI to CKD models on inflammation and fibrosis.
This study provides support for subtyping AKI by etiology in human studies, aiding in the elucidation of injury-specific pathophysiologic mechanisms of the AKI to CKD transition. PMID: 29897282 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Black L, Lever JM, Traylor AM, Chen B, Yang Z, Esman S, Jiang Y, Cutter G, Boddu R, George J, Agarwal A Tags: Am J Physiol Renal Physiol Source Type: research

Kir5.1 regulates Nedd4-2-mediated ubiquitination of Kir4.1 in distal nephron.
Abstract Kir4.1/5.1 heterotetramer participates in generating the negative cell membrane potential in distal convoluted tubule (DCT) and plays a critical role in determining the activity of Na-Cl co-transporter (NCC). Kir5.1 contains a phosphothreonine-motif at its c-terminus (AA249-252). Co-immunoprecipitation showed that Nedd4-2 was associated with Kir5.1 in HEK293 cells cotransfected with Kir5.1 or Kir4.1/Kir5.1. GST-pull-down further confirmed the association between Nedd4-2 and Kir5.1. Ubiquitination assay showed that Nedd4-2 increased the ubiquitination of Kir4.1/Kir5.1 heterotetramer in the cells co-transfe...
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Wang MX, Su XT, Wu P, Gao ZX, Wang WH, Staub O, Lin DH Tags: Am J Physiol Renal Physiol Source Type: research

NKA enhances bladder afferent mechanosensitivity via urothelial and detrusor activation.
Abstract Tachykinins are expressed within bladder innervating sensory afferents and have been shown to generate detrusor contraction and trigger micturition. The release of tachykinins from these sensory afferents may also activate tachykinin receptors on the urothelium, or sensory afferents directly. Here we investigated the direct and indirect influence of tachykinins on mechanosensation by recording sensory signalling from the bladder during distension, urothelial transmitter release ex-vivo, and direct responses to NKA on isolated mouse urothelial cells and bladder-innervating DRG neurons. Bath application of ...
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Grundy L, Chess-Williams R, Brierley SM, Mills K, Moore KH, Mansfield K, Rose'Meyer R, Sellers DJ, Grundy D Tags: Am J Physiol Renal Physiol Source Type: research

Return of the prorenin receptor: A novel role in macula dense signaling.
PMID: 29897285 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Ramkumar N Tags: Am J Physiol Renal Physiol Source Type: research

Heat Stress Nephropathy and Hyperuricemia.
PMID: 29897286 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Mattson DL Tags: Am J Physiol Renal Physiol Source Type: research

The Uroplakin Plaque Promotes Renal Structural Integrity During Congenital and Acquired Urinary Tract Obstruction.
In this study, we investigated the role of urothelial remodeling in renal adaptation during congenital and acquired obstruction. In the Megabladder ( Mgb-/-) model of congenital obstruction and unilateral ureteral ligation model of acute obstruction, progressive hydronephrosis is strongly associated with dynamic reorganization of the renal urothelium, which elaborates a continuous Uroplakin (Upk) plaque. This led us to postulate that the Upk plaque prevents parenchymal injury during urinary tract obstruction. To test this hypothesis, we interbred Mgb-/- and Upk1b-/- mice, which lack the critical Upk1b subunit for Upk plaqu...
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Jackson AR, Li B, Cohen SH, Ching CB, McHugh KM, Becknell B Tags: Am J Physiol Renal Physiol Source Type: research

Intermittent Hypoxia Exacerbates Increased Blood Pressure in Rats with Chronic Kidney Disease.
Abstract Kidney injury and sleep apnea (SA) are independent risk factors for hypertension. Exposing rats to intermittent hypoxia (IH) to simulate SA increases blood pressure while adenine feeding causes persistent kidney damage to model chronic kidney disease (CKD). We hypothesized that exposing CKD rats to IH would exacerbate the development of hypertension and renal failure. Male Sprague-Dawley rats were fed a 0.2% adenine or control diet until blood urea nitrogen (BUN) was > 120 mg/dL in adenine fed rats (14 {plus minus} 4 days). After two weeks recovery on normal chow, rats were exposed to IH (20 exposu...
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Riggs JL, Pace CE, Ward HH, Gonzalez Bosc LV, Rios L, Barrera A, Kanagy NL Tags: Am J Physiol Renal Physiol Source Type: research

The impact of Cannabidiol treatment on regulatory T-17 Cells and neutrophil polarization in Acute Kidney Injury.
Abstract Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory mechanisms culminating in tissue injury. Emerging information indicates heterogeneity of neutrophils with pro- and anti-inflammatory functions (N1 and N2, respectively). Also, regulatory T-17 (Treg17) cells curtail Th-17-mediated pro-inflammatory responses. However, the status of Treg17 cells and neutrophil phenotypes in AKI are not established. Further, cannabidiol exerts immunoregulatory effects but its impact on Treg17 cells and neutrophil subtypes is not established. Thus, we examined the status of Treg17 ce...
Source: Am J Physiol Renal P... - June 13, 2018 Category: Urology & Nephrology Authors: Baban B, Hoda MN, Malik A, Khodadadi H, Simmerman E, Vaibhav K, Mozaffari MS Tags: Am J Physiol Renal Physiol Source Type: research

Proteostasis as a Therapeutic Target in Glomerular Injury Associated with Mutant Alpha-Actinin-4.
Abstract Mutations in alpha-actinin-4 (actinin-4) result in hereditary focal segmental glomerulosclerosis (FSGS) in humans. Actinin-4 mutants induce podocyte injury due to dysregulation of the cytoskeleton and proteotoxicity. Injury may be associated with endoplasmic reticulum (ER) stress and polyubiquitination of proteins. We assessed if the chemical chaperone, 4-phenylbutyric acid (4-PBA) can ameliorate the proteotoxicity of an actinin-4 mutant. Actinin-4 K255E, which causes FSGS in humans (K256E in the mouse), showed enhanced ubiquitination, accelerated degradation, aggregate formation, and enhanced association...
Source: Am J Physiol Renal P... - June 6, 2018 Category: Urology & Nephrology Authors: Yee A, Papillon J, Guillemette J, Kaufman DR, Kennedy CRJ, Cybulsky AV Tags: Am J Physiol Renal Physiol Source Type: research

Sodium intake but not renal nerves attenuates renal venous pressure-induced changes in renal hemodynamics in rats.
Abstract Increased central venous pressure and renal venous pressure (RVP) is associated with worsening of renal function in acute exacerbation of congestive heart failure. We tested whether an acute, isolated elevation of RVP in one kidney leads to ipsilateral renal vasoconstriction and decreased GFR and whether this depends on dietary salt intake or activation of renal nerves. Male Lewis rats received a normal (1% NaCl, NS) or high salt diet (6% NaCl, HS) for {greater than or equal to}14 days before the acute experiment. Rats were then randomized into 3 groups: time control and RVP elevation to either 10 or 20 m...
Source: Am J Physiol Renal P... - June 6, 2018 Category: Urology & Nephrology Authors: Huang X, Hamza SM, Zhuang W, Cupples WA, Braam B Tags: Am J Physiol Renal Physiol Source Type: research

Adiponectin attenuates kidney injury and fibrosis in deoxycorticosterone acetate-salt and angiotensin II induced CKD mice.
Abstract Adiponectin (ApN) is a multifunctional adipokine. However high, rather than low, concentrations of ApN are unexpectedly found in patients with chronic kidney disease (CKD) via an as yet unknown mechanism and the role of ApN in CKD is unclear. We, herein, investigated the effect of ApN overexpression on the progressive renal injury resulted from deoxycorticosterone acetate-salt (DOCA) and angiotensin II (Ang-II) infusion using a transgenic, inducible ApN-overexpressing mouse model. Three groups of mice (wild type receiving no infusion (WT), WT and cyp1a1 ApN transgenic mice (ApN-Tg) receiving DOCA+Ang-II i...
Source: Am J Physiol Renal P... - June 6, 2018 Category: Urology & Nephrology Authors: Tian M, Tang L, Wu Y, Beddhu S, Huang Y Tags: Am J Physiol Renal Physiol Source Type: research

5-HT1F receptor regulates mitochondrial homeostasis and its loss potentiates acute kidney injury and impairs renal recovery.
Abstract Our laboratory previously reported that agonists of the 5-hydoxytryptamine 1F (5-HT1F) receptor induce renal mitochondrial biogenesis (MB) and that stimulation of the 5-HT1F receptor following ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) accelerated the recovery of renal function in mice. The goal of this study was to examine the contribution of the 5-HT1F receptor in the regulation of renal mitochondrial homeostasis and renal function in naïve and injured mice. While 5-HT1F receptor knockout (KO) mice were healthy and fertile, and did not exhibit renal dysfunction, renal mtDNA copy n...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Gibbs WS, Collier JB, Morris M, Beeson CC, Megyesi J, Schnellmann RG Tags: Am J Physiol Renal Physiol Source Type: research

Modulation of mean arterial pressure and diuresis by renomedullary infusion of a selective inhibitor of fatty acid amide hydrolase.
MODULATION OF MEAN ARTERIAL PRESSURE AND DIURESIS BY RENOMEDULLARY INFUSION OF A SELECTIVE INHIBITOR OF FATTY ACID AMIDE HYDROLASE. Am J Physiol Renal Physiol. 2018 May 30;: Authors: Ahmad A, Dempsey SK, Daneva Z, Li N, Poklis JL, Li PL, Ritter JK Abstract The kidneys contribute to the control of body fluid and electrolytes and the long-term regulation of blood pressure through various systems including the endocannabinoid system. Previously, we showed that inhibition of the two major endocannabinoid-hydrolyzing enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, in the renal medul...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Ahmad A, Dempsey SK, Daneva Z, Li N, Poklis JL, Li PL, Ritter JK Tags: Am J Physiol Renal Physiol Source Type: research

Kidney outer medulla mitochondria are more efficient compared to cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment.
Abstract The kidneys receive approximately 25% of cardiac output, which is a prerequisite in order to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic r...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Schiffer TA, Gustafsson H, Palm F Tags: Am J Physiol Renal Physiol Source Type: research

MicroRNA-132 controls water homeostasis through regulating MECP2-mediated vasopressin synthesis.
In conclusion, we identified miR-132 as a first miRNA regulating the osmo balance by regulating the hypothalamic AVP gene mRNA expression. PMID: 29846108 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Bijkerk R, Trimpert C, van Solingen C, de Bruin RG, Florijn BW, Kooijman S, van den Berg R, van der Veer EP, Bredewold EOW, Rensen PCN, Rabelink TJ, Humphreys BD, Deen PMT, van Zonneveld AJ Tags: Am J Physiol Renal Physiol Source Type: research

Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.
Abstract Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) al...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Fang H, Deng M, Zhang L, Lu A, Su J, Xu C, Zhou L, Wang L, Ou JS, Wang W, Yang T Tags: Am J Physiol Renal Physiol Source Type: research

Functional Implications of Sexual Dimorphism of Transporter Patterns along the Rat Proximal Tubule: Modeling and Analysis.
Abstract The goal of this study is to investigate the functional implications of the sexual dimorphism in transporter patterns along the proximal tubule. To do so, we have developed sex-specific computational models of solute and transport in the proximal convoluted tubule of the rat kidney. The models account for the sex differences in expression levels of the apical and basolateral transporters, in single-nephron glomerular filtration rate, and in tubular dimensions. Model simulations predict that 70.6 and 38.7% of the filtered volume is reabsorbed by the proximal tubule of the male and female rat kidneys, respe...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Li Q, McDonough AA, Layton HE, Layton AT Tags: Am J Physiol Renal Physiol Source Type: research

'First Do No Harm': Kidney Drug Targeting to Avoid Toxicity in ADPKD.
PMID: 29846111 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Chung EJ, Hallows KR Tags: Am J Physiol Renal Physiol Source Type: research

Prevention of the progression of renal injury in diabetic rodent models with pre-existing renal disease with chronic endothelin A receptor blockade.
Abstract The endothelin (ET) system has emerged as a therapeutic target for the treatment of diabetic nephropathy (DN). The present study examined whether chronic endothelin A (ETA) receptor blockade with atrasentan prevents the progression of renal injury in two models of DN with pre-existing renal disease that exhibit an increased renal ET-1 system compared to non-diabetic rats: streptozotocin-treated Dahl salt-sensitive (STZ-SS) and Type-2 diabetic nephropathy (T2DN) rats. Nine week-old SS rats were treated with (STZ, 50 mg/kg, i.p.) to induce diabetes. After 3 weeks of diabetes, proteinuria increased to 353{pl...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Spires D, Poudel B, Shields CA, Pennington A, Fizer B, Taylor L, McPherson KC, Cornelius DC, Williams JM Tags: Am J Physiol Renal Physiol Source Type: research

Mechanistic Target of Rapamycin (mTOR): Integrating Growth Factor and Nutrient Signaling in the Collecting Duct.
Abstract The renal collecting duct and other post-macula densa sites are the primary tubular regions for fine-tuning of electrolyte homeostasis in the body. A role for the mechanistic target of rapamycin (mTOR), a serine-threonine kinase, has recently been appreciated as playing a central role in this regulation. mTOR exists in two distinct multi-protein functional complexes, i.e., mTORC1 and mTORC2. Upregulation of mTORC1, by growth factors and amino acids, is associated with cell cycle regulation and hypertrophic changes in the cell. In contrast, mTORC2 has been demonstrated to have a role in regulating sodium a...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Brown A, Fluitt MB, Ecelbarger CM Tags: Am J Physiol Renal Physiol Source Type: research

Kidney dysfunction in the low birth weight murine adult: implications of oxidative stress.
In conclusion, despite some minor differences, LBW female and male adults that have a reduced nephron endowment experience comparable progressive renal and vascular dysfunction that is associated with increased oxidative stress and subsequent endothelial dysfunction. Tempol treatment and/or NOX4 inhibition attenuates renal and vascular dysfunction in LBW adults. PMID: 29846114 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Abdulmahdi W, Rabadi MM, Jules E, Marghani Y, Marji N, Leung J, Zhang FF, Siani A, Siskind T, Vedovino K, Chowdhury N, Sekulic M, Ratliff BB Tags: Am J Physiol Renal Physiol Source Type: research

A Model of Calcium Transport and Regulation in the Proximal Tubule.
The objective of this study was to examine theoretically how Ca2+ reabsorption in the proximal tubule (PT) is modulated by Na+ and water fluxes, parathyroid hormone (PTH), SGLT2 inhibitors, and acetazolamide. To do so, we expanded a previously published mathematical model of water and solute transport in the rat PT (Layton AT, Vallon V, and Edwards A. Am J Physiol Renal Physiol 308: F1343-F1357, 2015) that did not include Ca2+. Our results indicate that Ca2+ reabsorption in the PT is primarily driven by the transepithelial Ca2+ concentration gradient that stems from water reabsorption, which is itself coupled to Na+ reabso...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Edwards A, Bonny O Tags: Am J Physiol Renal Physiol Source Type: research

Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC.
DH, Gamba G Abstract Familial Hyperkalemic Hypertension (FHHt) can be mainly attributed to increased activity of the renal Na+:Cl- cotransporter (NCC), which is caused by altered expression and regulation of the WNK1 and WNK4 kinases. The WNK1 gene gives rise to a kidney-specific isoform that lacks the kinase domain (KS-WNK1), the expression of which occurs primarily in the distal convoluted tubule. The role played by KS-WNK1 in the modulation of the WNK/SPAK/NCC pathway remains elusive. In the present study, we assessed the effect of human KS-WNK1 on NCC activity and on the WNK4-SPAK pathway. Microinjection of oo...
Source: Am J Physiol Renal P... - May 30, 2018 Category: Urology & Nephrology Authors: Argaiz ER, Chavez-Canales M, Ostrosky-Frid M, Rodriguez-Gama A, Vázquez N, Gonzalez-Rodriguez X, Garcia-Valdés J, Hadchouel J, Ellison DH, Gamba G Tags: Am J Physiol Renal Physiol Source Type: research

Graft function assessment in mouse models of single- and dual- kidney transplantation.
In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease. PMID: 29790388 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 23, 2018 Category: Urology & Nephrology Authors: Wang L, Wang X, Jiang S, Wei J, Buggs J, Fu L, Zhang J, Liu R Tags: Am J Physiol Renal Physiol Source Type: research

Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat.
In conclusion, SGLT2 inhibition induces a sustained diuretic and natriuretic tone. Homeostatic mechanisms are activated to stabilize body fluid volume, including compensatory increases in fluid and food intake. PMID: 29790389 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 23, 2018 Category: Urology & Nephrology Authors: Masuda T, Watanabe Y, Fukuda K, Watanabe M, Onishi A, Ohara K, Imai T, Koepsell H, Muto S, Vallon V, Nagata D Tags: Am J Physiol Renal Physiol Source Type: research

Collecting duct principal, but not intercalated, cell prorenin receptor regulates renal sodium and water excretion.
COLLECTING DUCT PRINCIPAL, BUT NOT INTERCALATED, CELL PRORENIN RECEPTOR REGULATES RENAL SODIUM AND WATER EXCRETION. Am J Physiol Renal Physiol. 2018 May 23;: Authors: Ramkumar N, Stuart D, Mironova E, Abraham N, Gao Y, Wang S, Lakshmipathi J, Stockand JD, Kohan DE Abstract The collecting duct is the predominant nephron site of prorenin and prorenin receptor (PRR) expression. We previously demonstrated that the collecting duct PRR regulates epithelial Na+ channel (ENaC) activity and water transport; however, which cell type is involved remains unclear. Herein, we examined the effects of principal cell ...
Source: Am J Physiol Renal P... - May 23, 2018 Category: Urology & Nephrology Authors: Ramkumar N, Stuart D, Mironova E, Abraham N, Gao Y, Wang S, Lakshmipathi J, Stockand JD, Kohan DE Tags: Am J Physiol Renal Physiol Source Type: research

Neutrophil exocytosis induces podocyte cytoskeletal reorganization and proteinuria in experimental glomerulonephritis.
Abstract Acute glomerulonephritis is characterized by rapid glomerular neutrophil recruitment, proteinuria, and glomerular hypercellularity. The current study tested the hypothesis that release of neutrophil granule contents plays a role in both loss of filtration barrier leading to proteinuria and the increase in glomerular cells. Inhibition of neutrophil exocytosis with a peptide inhibitor prevented proteinuria and attenuated podocyte and endothelial cell injury, but had no effect on glomerular hypercellularity in an experimental acute glomerulonephritis model in mice. Cultivation of podocytes with neutrophil gr...
Source: Am J Physiol Renal P... - May 23, 2018 Category: Urology & Nephrology Authors: Caster DJ, Korte EA, Tan M, Barati MT, Tandon S, Creed TM, Salant DJ, Hata JL, Epstein PN, Huang H, Powell DW, McLeish KR Tags: Am J Physiol Renal Physiol Source Type: research

Interleukin 1 Receptor (IL-1R1) Activation Exacerbates Toxin-Induced Acute Kidney Injury.
Abstract Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Cisplatin is an effective chemotherapeutic agent whose administration is limited by nephrotoxicity. Therapies to prevent cisplatin-induced AKI are lacking. While tumor necrosis factor-α (TNF) plays a key role in the pathogenesis of cisplatin nephrotoxicity, the immune signaling pathways that trigger TNF generation in this context require elucidation. Sterile injury triggers the release and activation of both isoforms of interleukin(IL)-1, IL-1α and IL-1β, and stimulation of the interleukin-1 receptor (IL-1R1) by thes...
Source: Am J Physiol Renal P... - May 23, 2018 Category: Urology & Nephrology Authors: Privratsky JR, Zhang J, Lu X, Rudemiller N, Wei Q, Yu YR, Gunn MD, Crowley SD Tags: Am J Physiol Renal Physiol Source Type: research

Protective effect of the BET protein inhibitor JQ1 in cisplatin-induced nephrotoxicity.
Abstract As a potent chemotherapy drug, cisplatin is also notorious for its side effects including nephrotoxicity in kidneys, presenting a pressing need to identify renoprotective agents. Cisplatin nephrotoxicity involves epigenetic regulations, including changes in histone acetylation. Bromodomain and extra-terminal (BET) proteins are "readers" of the epigenetic code of histone acetylation. Here, we investigated the potential renoprotective effects of JQ1, a small molecule inhibitor of BET proteins. We show that JQ1 significantly ameliorated cisplatin-induced nephrotoxicity in mice as indicated by the m...
Source: Am J Physiol Renal P... - May 16, 2018 Category: Urology & Nephrology Authors: Sun L, Liu J, Yuan Y, Zhang X, Dong Z Tags: Am J Physiol Renal Physiol Source Type: research

Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and γ-ENaC abundance in rat kidney.
This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na+ transporters; and iii) the injured UPJO kidney allows aberrant filtration of plasminogen leading to proteolytic activation of the epithelial sodium channel gamma subunit (γ-ENaC). Hydronephrosis due to UPJO in pediatric patients and rats was associated with increased urinary plasminogen/creatinine ratio. In pediatric patients, plasma renin, angiotensin...
Source: Am J Physiol Renal P... - May 16, 2018 Category: Urology & Nephrology Authors: Zachar R, Al-Mashhadi A, Dimke H, Svenningsen P, Jensen BL, Carlström M Tags: Am J Physiol Renal Physiol Source Type: research

Polycystin-1 dysfunction impairs electrolyte and water handling in a renal pre-cystic mouse model for adpkd.
In conclusion, our data indicate that PC1 is involved in renal Mg2+, Ca2+ and water handling, and its dysfunction resulting in a systemic electrolyte imbalance characterized by low serum electrolyte concentrations. PMID: 29767557 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 16, 2018 Category: Urology & Nephrology Authors: Verschuren EHJ, Mohammed SG, Leonhard WN, Overmars-Bos C, Veraar KAM, Hoenderop JGJ, Bindels RJM, Peters DJM, Arjona FJ Tags: Am J Physiol Renal Physiol Source Type: research

Molecular basis of the counteraction by calcium channel blockers of Cyclosporine nephrotoxicity.
In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorate renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats (n=6/group) were used and received one of the following treatments for 7 consecutive days: vehicle (cremophor EL, i.p.), CSA (25 mg.kg-1.day-1, i.p.), verapamil (2 mg.kg-1.day-1, i.p.), nifedipine (3 mg.kg-1.day-1, i.p.), CSA in the presence or absence of either verapamil, or nifedipine. Biochemical and his...
Source: Am J Physiol Renal P... - May 16, 2018 Category: Urology & Nephrology Authors: Hammoud SH, Alkhansa S, Mahjoub N, Omar AG, El-Mas MM, Eid AA Tags: Am J Physiol Renal Physiol Source Type: research

G-protein Pathway Suppressor 2 (GPS2) enhanced the renal large conductance Ca2+ activated potassium channel expression via inhibiting ERK 1/2 signaling pathway.
In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. In HEK BK stably-expressing cells transfected with either GPS2 or its pCMV vector control, a single cell recording showed that GPS2 significantly increased BK channel activity (NPo), increasing BK open probability (Po) and channel number (N) compared to the control. In Cos-7 cells and HEK293T cells, GPS2 overexpression significantly enhanced the total protein expression of BK in a dose-dependent manner. Knockdown of GPS2 expression significantly decreased BK protein expression while increasing ERK1/2 phosphorylation. Knockdown...
Source: Am J Physiol Renal P... - May 16, 2018 Category: Urology & Nephrology Authors: Zhuang Z, Xiao J, Chen X, Hu X, Li R, Chen S, Feng X, Shen S, Ma HP, Zhuang J, Cai H Tags: Am J Physiol Renal Physiol Source Type: research

Monophosphoryl lipid A prevents impairment of medullary thick ascending LIMB HCO3- absorption and improves plasma HCO3- concentration in septic mice.
Abstract Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs HCO3- absorption in the MTAL by: 1) decreasing the intrinsic HCO3- absorptive capacity, and 2) enhancing inhibition of HCO3- absorption by LPS through upregulation of TLR4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis. Pretreatment of MTALs with MPLA in ...
Source: Am J Physiol Renal P... - May 9, 2018 Category: Urology & Nephrology Authors: Watts BA, George T, Sherwood ER, Good DW Tags: Am J Physiol Renal Physiol Source Type: research

Expression of the B splice variant of NBCe1 (SLC4A4) in the mouse kidney.
This study's purpose was to determine if there is expression of additional NBCe1 splice variants in the mouse kidney, their cellular distribution and their regulation by metabolic acidosis. In wild-type (WT) mice an antibody reactive only to NBCe1-A showed basolateral immunolabel only in cortical proximal tubule (PT) segments, whereas an antibody reactive to all NBCe1 splice variants (pan-NBCe1) showed basolateral immunolabel in PT segments in both the cortex and outer medulla. In mice with NBCe1-A deletion the pan-NBCe1 antibody showed basolateral PT immunolabel in both the renal cortex and outer stripe of the outer medul...
Source: Am J Physiol Renal P... - April 4, 2018 Category: Urology & Nephrology Authors: Fang L, Lee HW, Chen C, Harris AN, Romero MF, Verlander JW, Weiner ID Tags: Am J Physiol Renal Physiol Source Type: research

Sphingosine-1-Phosphate Pathway in Renal Fibrosis.
Abstract Renal fibrosis is defined as the excessive deposition and modification of extracellular matrix (ECM) in the renal parenchyma in response to injury and inflammation, resulting in renal function loss. This condition is common to many chronic kidney diseases (CKD) that occur under diverse pathological conditions, such as diabetic and hypertensive nephropathy. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in regulation of cardiovascular functions and pathogenesis of various cardiovascular diseases. S1P has also been seen as an important regulator of fibrotic diseases, playing s...
Source: Am J Physiol Renal P... - April 4, 2018 Category: Urology & Nephrology Authors: Zhang X, Ritter JK, Li N Tags: Am J Physiol Renal Physiol Source Type: research

Vimentin expression is required for the development of EMT-related renal fibrosis following Unilateral Ureteral Obstruction in mice.
Abstract Most renal transplants ultimately fail secondary to chronic allograft nephropathy (CAN). Vimentin is a member of the intermediate filament family of proteins and has been shown to be important in the development of CAN. One of the pathways leading to chronic renal fibrosis after transplant is thought to be Epithelial to Mesenchymal Transition (EMT). Even though vimentin expression is one of the main steps during EMT, it is unknown whether vimentin expression is required for EMT. To this end, the role of vimentin in renal fibrosis was determined via unilateral ureteral obstruction (UUO) in vimentin knockou...
Source: Am J Physiol Renal P... - April 4, 2018 Category: Urology & Nephrology Authors: Wang Z, Divanyan A, Jourd'heuil F, Goldman RD, Ridge KM, Jourd'heuil D, Lopez-Soler RI Tags: Am J Physiol Renal Physiol Source Type: research

Comparison of potential dietary and urinary risk factors for ammonium urate nephrolithiasis in two bottlenose dolphin (Tursiops truncatus) populations.
In this study, urine samples were collected from 16 dolphins (8 cases, 8 controls) from the U.S. Navy Marine Mammal Program (MMP) for the purposes of assessing changes in urinary biomarkers after a large meal. Urinary biomarkers and nephrolithiasis presence were assessed opportunistically in 15 long-term resident free-ranging dolphins living in Sarasota Bay, Florida (SB). Additionally, the total purine contents of fish commonly consumed by each dolphin population were measured to evaluate potential dietary risk factors. Populations were compared for total dietary purine composition, recently fed status, nephrolithiasis pre...
Source: Am J Physiol Renal P... - April 4, 2018 Category: Urology & Nephrology Authors: Le-Bert CR, Smith CR, Poindexter J, Ardente A, Meegan J, Wells RS, Venn-Watson S, Jensen ED, Sakhaee K Tags: Am J Physiol Renal Physiol Source Type: research

Loss of biliverdin reductase-A (BVRA) promotes lipid accumulation and lipotoxicity in mouse proximal tubule cells.
Abstract Obesity and increased lipid availability have been implicated in the development and progression of chronic kidney disease. One of the major sites of renal lipid accumulation is in the proximal tubule cells of the kidney, suggesting that these cells may be susceptible to lipotoxicity. We previously demonstrated that loss of hepatic BVRA causes fat accumulation in livers of mice on a high-fat diet. To determine the role of BVRA in mouse proximal tubule cells, we generated a CRISPR targeting BVRA for a knock-out in mouse MCT proximal tubule cells (BVRA KO). The BVRA-KO cells had significantly less metabolic...
Source: Am J Physiol Renal P... - April 4, 2018 Category: Urology & Nephrology Authors: Adeosun SO, Gordon DM, Weeks MF, Moore KH, Hall JE, Hinds TD, Stec DE Tags: Am J Physiol Renal Physiol Source Type: research

Na+-Cl- cotransporter-mediated chloride uptake contributes to hypertension and renal damage in aldosterone-infused rats.
Abstract Recently, in addition to epithelial sodium channel alpha-subunit (αENaC), the thiazide-sensitive sodium-chloride cotransporter (NCC) and pendrin, also known as sodium-independent chloride/iodide transporter, were reported to be activated by aldosterone. Here, we investigated whether chloride (Cl-) is responsible for hypertension, inflammation, and renal damage in aldosterone-infused rats. Following left nephrectomy, 8-week-old male Sprague-Dawley rats were allocated into four groups: 1) drinking 1.0% sodium chloride solution with aldosterone infusion (Aldo/NaCl rats); 2) drinking 1.44% sodium bicarb...
Source: Am J Physiol Renal P... - April 4, 2018 Category: Urology & Nephrology Authors: Yamauchi T, Doi S, Nakashima A, Doi T, Sohara E, Uchida S, Masaki T Tags: Am J Physiol Renal Physiol Source Type: research

Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response.
Abstract The homeobox transcription factor Meis1 is required for mammalian development and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease, and tested this using cell lineage tracing and cell specific Meis1 deletion in development, aging and fibrotic disease. We observed strong expression of Meis1 in PDGFRβ positive pericytes and perivascular fibroblasts, both in adult mouse and to a lesser degree i...
Source: Am J Physiol Renal P... - March 28, 2018 Category: Urology & Nephrology Authors: Chang-Panesso M, Kadyrov FF, Machado FG, Kumar A, Humphreys BD Tags: Am J Physiol Renal Physiol Source Type: research

Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats.
In conclusion, Mel+CA treatment caused urine concentrating defect and reduced expression of renal AQPs and key sodium transporters, which is likely due to the inflammatory responses and activation of NLRP3 inflammasome induced by crystals formed in the kidney. PMID: 29592526 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 28, 2018 Category: Urology & Nephrology Authors: Wang F, Liu Q, Jin L, Hu S, Luo R, Han M, Zhai Y, Wang W, Li C Tags: Am J Physiol Renal Physiol Source Type: research

Generation, clearance, toxicity and monitoring possibilities of unaccounted uremic toxins for improved dialysis prescriptions.
Abstract Current dialysis dosing calculations provide an incomplete assessment of blood purification. They do not include clearances of protein-bound uremic toxins like polyamines, p-cresol sulfate, and indoxyl sulfate, relying solely on the clearance of urea as a surrogate for all molecules accumulating in patients with end stage renal disease (ESRD). Protein-bound uremic toxins clear differently in dialysis but also during normal renal function. The kidney clears protein bound toxins via the process of secretion, while it clears urea through filtration. Herein we review the clearance, accumulation, and toxicity ...
Source: Am J Physiol Renal P... - March 14, 2018 Category: Urology & Nephrology Authors: Atherton JG, Hains DS, Bissler JJ, Pendley BD, Lindner E Tags: Am J Physiol Renal Physiol Source Type: research

Casein kinase 1 ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8.
Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8. Am J Physiol Renal Physiol. 2018 Mar 14;: Authors: Billot K, Coquil C, Villiers B, Josselin-Foll B, Desban N, Delehouze C, Oumata N, Le Meur Y, Boletta A, Weimbs T, Grosch M, Witzgall R, Saunier S, Fischer E, Pontoglio M, Fautrel A, Mrug M, Wallace DP, Tran PV, Trudel M, Bukanov NO, Ibraghimov-Beskrovnaya O, Meijer L Abstract Following the discovery of (R)-roscovitine's beneficial effects in three polycystic kidney disease (PKD) mouse models, cyclin-dependent kin...
Source: Am J Physiol Renal P... - March 14, 2018 Category: Urology & Nephrology Authors: Billot K, Coquil C, Villiers B, Josselin-Foll B, Desban N, Delehouze C, Oumata N, Le Meur Y, Boletta A, Weimbs T, Grosch M, Witzgall R, Saunier S, Fischer E, Pontoglio M, Fautrel A, Mrug M, Wallace DP, Tran PV, Trudel M, Bukanov NO, Ibraghimov-Beskrovnaya Tags: Am J Physiol Renal Physiol Source Type: research

A zebrafish model of infection-associated acute kidney injury.
Abstract Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish (Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for sepsis-associated AKI research. We introduced Edwardsiella tarda (E.tarda) to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune rea...
Source: Am J Physiol Renal P... - March 14, 2018 Category: Urology & Nephrology Authors: Wen X, Cui L, Morrisroe S, Maberry D, Emlet DR, Watkins SC, Hukriede NA, Kellum JA Tags: Am J Physiol Renal Physiol Source Type: research

Predicted Effect of Circadian Clock Modulation of NHE3 of a Proximal Tubule Cell on Sodium Transport.
Abstract Major renal functions such as renal blood flow, glomerular filtration rate, and urinary excretion are known to exhibit circadian oscillations. However, the underlying mechanisms that govern these variations have yet to be fully elucidated. To better understand the impact of the circadian clock on renal solute and water transport, we have developed a computational model of the renal circadian clock, and coupled that model to an epithelial transport model of the proximal convoluted cell of the rat kidney. The activity of the Na$^+$-H$^+$ exchanger 3 (NHE3) is assumed to be regulated by changes in transcript...
Source: Am J Physiol Renal P... - March 14, 2018 Category: Urology & Nephrology Authors: Wei N, Gumz ML, Layton AT Tags: Am J Physiol Renal Physiol Source Type: research

Glucose Dilates Renal Afferent Arterioles via Glucose Transporter-1.
In conclusion, we demonstrated that an increase in glucose concentration dilates the Af-Art by stimulation of the endothelium derived NO production mediated by GLUT1. PMID: 29513069 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 7, 2018 Category: Urology & Nephrology Authors: Zhang J, Jiang S, Wei J, Yip KP, Wang L, Lai EY, Liu R Tags: Am J Physiol Renal Physiol Source Type: research