5,912 results match your criteria American Journal of Physiology - Renal Physiology[Journal]


By the way, proximal tubule calcium transport.

Authors:
Alan M Weinstein

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

Department of Physiology and Biophysics, Weill Medical College of Cornell University, United States.

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Intrarenal Toll-like receptor 4 and Toll-like receptor 2 expression correlates with injury in anti-neutrophil cytoplasmic antibody associated vasculitis.

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

Department of Medicine, Monash Institute of Medical Research, Victoria, Australia, Australia.

In anti-neutrophil cytoplasmic antibody associated vasculitis (AAV), toll like receptors (TLRs) may be engaged by infection associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4 and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4 and TLR9, with TLR4 being the most prominent in both compartments. Read More

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INTRARENAL GHRELIN RECEPTOR INHIBITION AMELIORATES ANGIOTENSIN II-DEPENDENT HYPERTENSION IN RATS.

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

Internal Medicine, Endocrinology and Metabolism, University of Virginia School of Medicine, United States.

The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Read More

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June 2018
2 Reads

The protective role of Trpc6 knockout in the progression of diabetic kidney disease.

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

Physiology, Medical College of Wisconsin, United States.

Diabetic kidney disease (DKD) is a chronic kidney pathology that leads to end stage renal disease. Previous studies from our laboratory indicate that there is an association between the development of DKD and the TRPC6 channel. Trpc6 expression and activity was increased in the streptozotocin (STZ)-treated Dahl Salt-sensitive (SS) rat, an established model of type 1 diabetes. Read More

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June 2018
1 Read

WNK-SPAK/OSR1 signaling: lessons learned from an insect renal epithelium.

Authors:
Aylin R Rodan

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah Molecular Medicine Program, University of Utah, United States.

WNK (With No Lysine (K)) kinases regulate renal epithelial ion transport to maintain homeostasis of electrolyte concentrations, extracellular volume and blood pressure. The SLC12 cation-chloride cotransporters, including the sodium-potassium-2-chloride (NKCC) and sodium-chloride (NCC) cotransporters, are targets of WNK regulation via the intermediary kinases SPAK (Ste20-related proline/alanine-rich kinase) and OSR1 (oxidative stress response). The pathway is activated by low dietary potassium intake, resulting in increased phosphorylation and activity of NCC. Read More

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Physiological functions of Ferroportin in the regulation of renal iron recycling and ischemic acute kidney injury.

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

School of Life Sciences and Technology, Tongji University, China.

Renal iron recycling preserves the filtered iron from urinary excretion. However, it remains debated whether ferroportin (FPN), the solely known iron exporter, is functionally involved in renal iron recycling, and whether renal iron recycling is required for systemic iron homeostasis. We deleted FPN in the whole nephrons using a Nestin-Cre and in the distal nephrons and collecting ducts using a Ksp-Cre, and investigated its impacts on renal iron recycling and systemic iron homeostasis. Read More

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June 2018
2 Reads

Regulation of Renal Na Transporters in Response to Dietary K.

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

Physiology and Biophysics, Weill-Cornell Medical College, United States.

Changes in the expression of Na transport proteins were measured in the kidneys of mice with increased dietary K intake for 1 week. The epithelial Na channel (ENaC) was upregulated, with enhanced expression of full-length and cleaved forms of αENaC and cleaved γENaC. At the same time, the amount of the NaCl cotransporter (NCC) and its phosphorylated form decreased by ~50% and ~80% respectively. Read More

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NOVEL HAEMODYNAMIC STRUCTURES IN THE HUMAN GLOMERULUS.

Am J Physiol Renal Physiol 2018 Jun 20. Epub 2018 Jun 20.

Physiology and Pharmacology, University of Bristol.

To investigate human glomerular structure under conditions of physiological perfusion we have analysed fresh and perfusion fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, confocal, multiphoton and electron microscope imaging. Afferent and efferent arterioles (21.5{plus minus}1. Read More

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The impact of Cannabidiol treatment on regulatory T-17 Cells and neutrophil polarization in Acute Kidney Injury.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Oral Biology, Augusta University.

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. Read More

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June 2018
1 Read

Intermittent Hypoxia Exacerbates Increased Blood Pressure in Rats with Chronic Kidney Disease.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Cell Biology and Physiology, University of New Mexico School of Medicine, United States.

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. Read More

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June 2018
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The Uroplakin Plaque Promotes Renal Structural Integrity During Congenital and Acquired Urinary Tract Obstruction.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, United States.

Urinary tract obstruction represents a common cause of kidney injury across the human lifespan, resulting in chronic kidney disease and end stage renal disease. Yet the extent of obstructive renal damage can be heterogeneous between individuals, implying the existence of unknown mechanisms that protect against or accelerate kidney injury. In this study, we investigated the role of urothelial remodeling in renal adaptation during congenital and acquired obstruction. Read More

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June 2018
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Heat Stress Nephropathy and Hyperuricemia.

Authors:
David L Mattson

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Physiology, Medical College of Wisconsin, United States.

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Return of the prorenin receptor: A novel role in macula dense signaling.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Division of Nephrology, University of Utah, United States.

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NKA enhances bladder afferent mechanosensitivity via urothelial and detrusor activation.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Biomedical Science, University of Sheffield, United Kingdom.

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. Read More

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Kir5.1 regulates Nedd4-2-mediated ubiquitination of Kir4.1 in distal nephron.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Pharmacology, New York Medical College, United States.

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). Read More

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Divergent effects of AKI to CKD models on inflammation and fibrosis.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Medicine, University of Alabama at Birmingham, United States.

Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis. Read More

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Autophagy activation in circulating proangiogenic cells (PACs) aggravates AKI in type I diabetes mellitus.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Department of Cardiology, Pulmology, Angiology, Nephrology, Medizinische Hochschule Brandenburg, Germany.

Background: AKI (Acute Kidney Injury) occurs frequently in hospitals worldwide, the therapeutic options are limited. Diabetes mellitus (DM) affects more and more people around the globe, the disease worsens the prognosis of AKI even further. In recent years, cell-based therapies have increasingly been applied in experimental AKI. Read More

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June 2018
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Dual gain and loss of cullin 3 function mediates familial hyperkalemic hypertension.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

OCTRI, Oregon Health and Science University, United States.

Familial hyperkalemic hypertension is caused by mutations in WNK kinases, or in proteins that mediate their degradation, KLHL3 and cullin 3 (Cul3). While the mechanisms by which WNK and KLHL3 mutations cause the disease are now clear, the effects of the disease-causing Cul3Δ403-459 mutation remain controversial. Possible mechanisms including hyperneddylation, altered ubiquitin ligase activity, decreased association with the COP9 signalosome (CSN), and increased association with and degradation of KLHL3 have all been postulated. Read More

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Vascular Type 1 Angiotensin Receptors Control Blood Pressure by Augmenting Peripheral Vascular Resistance in Female Mice.

Am J Physiol Renal Physiol 2018 Jun 13. Epub 2018 Jun 13.

Department of Medicine, Duke University and Durham VA Medical Centers, United States.

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. Read More

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Adiponectin attenuates kidney injury and fibrosis in deoxycorticosterone acetate-salt and angiotensin II induced CKD mice.

Am J Physiol Renal Physiol 2018 Jun 6. Epub 2018 Jun 6.

Nephrology & Hypertension, university of Utah Health, United States.

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. Read More

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Sodium intake but not renal nerves attenuates renal venous pressure-induced changes in renal hemodynamics in rats.

Am J Physiol Renal Physiol 2018 Jun 6. Epub 2018 Jun 6.

Division of Nephrology and Immunology, University of Alberta, Canada.

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. Read More

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Proteostasis as a Therapeutic Target in Glomerular Injury Associated with Mutant Alpha-Actinin-4.

Am J Physiol Renal Physiol 2018 Jun 6. Epub 2018 Jun 6.

Medicine, McGill University, Canada.

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. Read More

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Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Mexico.

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. Read More

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A Model of Calcium Transport and Regulation in the Proximal Tubule.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Dpt of Pharmacology and Toxicology, University of Lausanne, Switzerland.

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+. Read More

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Kidney dysfunction in the low birth weight murine adult: implications of oxidative stress.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Medicine, Physiology, New York Medical College, United States.

Maternal undernutrition during pregnancy leads to low birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 months of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy and a worse survival rate than LBW females. Read More

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May 2018
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Mechanistic Target of Rapamycin (mTOR): Integrating Growth Factor and Nutrient Signaling in the Collecting Duct.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Medicine, Georgetown University, United States.

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. Read More

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Prevention of the progression of renal injury in diabetic rodent models with pre-existing renal disease with chronic endothelin A receptor blockade.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Pharmacology and Toxicology, University of Mississippi Medical Center, United States.

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. Read More

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'First Do No Harm': Kidney Drug Targeting to Avoid Toxicity in ADPKD.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Medicine, Division of Nephrology and Hypertension, University of Southern California, United States.

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Functional Implications of Sexual Dimorphism of Transporter Patterns along the Rat Proximal Tubule: Modeling and Analysis.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Department of Mathematics, Duke University, United States.

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. Read More

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Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Internal Medicine, University of Utah and Veteran Affairs Medical Center, United States.

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. Read More

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May 2018
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MicroRNA-132 controls water homeostasis through regulating MECP2-mediated vasopressin synthesis.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Department of Nephrology and the Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center.

Fine-tuning of the body's water balance is regulated by vasopressin (AVP), which induces the expression and apical membrane insertion of aquaporin-2 water channels and subsequent water reabsorption in the kidney. Here we demonstrate that silencing of microRNA-132 in mice causes severe weight loss due to acute diuresis coinciding with increased plasma osmolality, reduced renal total and plasma membrane expression of aquaporin-2 and abrogated increase in AVP levels. Infusion with synthetic AVP fully reversed the antagomir-132 induced diuresis and low-dose intracerebroventricular administration of antagomir-132 similarly caused acute diuresis. Read More

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Kidney outer medulla mitochondria are more efficient compared to cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Medical Cell Biology, Uppsala University, Sweden.

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. Read More

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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. Epub 2018 May 30.

Pharmacology and Toxicology, Virginia Commonwealth Univ, United States.

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 medulla increased the rate of urine excretion (UV) and salt excretion without affecting mean arterial pressure (MAP). The present study evaluated the effects of a selective FAAH inhibitor, PF-3845 (N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidine carboxamide) on MAP and renal functions. Read More

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5-HT1F receptor regulates mitochondrial homeostasis and its loss potentiates acute kidney injury and impairs renal recovery.

Am J Physiol Renal Physiol 2018 May 30. Epub 2018 May 30.

Pharmaceutical Sciences, Medical University of South Carolina, United States.

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 number and mitochondrial fission gene expression increased at 10 weeks of age. Read More

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Interleukin 1 Receptor (IL-1R1) Activation Exacerbates Toxin-Induced Acute Kidney Injury.

Am J Physiol Renal Physiol 2018 May 23. Epub 2018 May 23.

Medicine, Duke University, United States.

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. Read More

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Neutrophil exocytosis induces podocyte cytoskeletal reorganization and proteinuria in experimental glomerulonephritis.

Am J Physiol Renal Physiol 2018 May 23. Epub 2018 May 23.

Kidney Disease Program, University of Louisville, United States.

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. Read More

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COLLECTING DUCT PRINCIPAL, BUT NOT INTERCALATED, CELL PRORENIN RECEPTOR REGULATES RENAL SODIUM AND WATER EXCRETION.

Am J Physiol Renal Physiol 2018 May 23. Epub 2018 May 23.

Division of Nephrology, University of Utah Health Sciences Center, United States.

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 (PC) or intercalated cell (IC) PRR deletion on renal Na+ and water handling. Read More

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May 2018
2 Reads

Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat.

Am J Physiol Renal Physiol 2018 May 23. Epub 2018 May 23.

Division of Nephrology, Department of Internal Medicine, Jichi Medical University.

The chronic intrinsic diuretic and natriuretic tone of sodium-glucose cotransporter 2 (SGLT2) inhibitors is incompletely understood, because their effect on body fluid volume (BFV) has not been fully evaluated and because they often increase food and fluid intake at the same time. Here we first compared the effect of the SGLT2 inhibitor ipragliflozin (Ipra, 0.01% in diet for 8 weeks) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a non-obese type 2 diabetic model, and non-diabetic Sprague-Dawley rats. Read More

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Graft function assessment in mouse models of single- and dual- kidney transplantation.

Am J Physiol Renal Physiol 2018 May 23. Epub 2018 May 23.

Molecular Pharmacology and Physiology, University of South Flroida College of Medicine, United States.

Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild type recipients or vise verse. Dual kidney transplantation (DKT) provides a more physiological environment for recipients than single kidney transplantation (SKT). Read More

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G-protein Pathway Suppressor 2 (GPS2) enhanced the renal large conductance Ca2+ activated potassium channel expression via inhibiting ERK 1/2 signaling pathway.

Am J Physiol Renal Physiol 2018 May 16. Epub 2018 May 16.

Medicine/Renal, Emory University School of Medicine, United States.

G-protein pathway suppressor 2 (GPS2) is a multifunctional protein and transcriptional regulation factor that is involved in the G-protein mitogen-activated protein kinase (MAPK) signaling pathway. It has been shown that the MAPK signaling pathway plays an important role in the regulation of renal large conductance Ca2+ activated potassium (BK) channels. In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. Read More

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Molecular basis of the counteraction by calcium channel blockers of Cyclosporine nephrotoxicity.

Am J Physiol Renal Physiol 2018 May 16. Epub 2018 May 16.

Anatomy, Cell Biology and Physiological Sciences, American university of Beirut, Lebanon.

Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine (CSA). 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. Read More

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POLYCYSTIN-1 DYSFUNCTION IMPAIRS ELECTROLYTE AND WATER HANDLING IN A RENAL PRE-CYSTIC MOUSE MODEL FOR ADPKD.

Am J Physiol Renal Physiol 2018 May 16. Epub 2018 May 16.

Physiology, Radboud university medical center, Netherlands.

The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. Read More

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Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and γ-ENaC abundance in rat kidney.

Am J Physiol Renal Physiol 2018 May 16. Epub 2018 May 16.

Physiology and Pharmacology, Karolinska Institutet, Sweden.

Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. 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). Read More

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Protective effect of the BET protein inhibitor JQ1 in cisplatin-induced nephrotoxicity.

Am J Physiol Renal Physiol 2018 May 16. Epub 2018 May 16.

Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, United States.

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. Read More

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May 2018
1 Read

Monophosphoryl lipid A prevents impairment of medullary thick ascending LIMB HCO absorption and improves plasma HCO concentration in septic mice.

Am J Physiol Renal Physiol 2018 May 9. Epub 2018 May 9.

Medicine and Neuroscience & Cell Biology, The University of Texas Medical Branch, United States.

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 HCO absorption in the MTAL by: 1) decreasing the intrinsic HCO absorptive capacity, and 2) enhancing inhibition of HCO absorption by LPS through upregulation of TLR4 signaling. Both effects depend on ERK activation. Read More

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Comparison of folate-conjugated rapamycin versus unconjugated rapamycin in an orthologous mouse model of polycystic kidney disease.

Am J Physiol Renal Physiol 2018 May 2. Epub 2018 May 2.

Department of Molecular, Cellular & Developmental Biology, University of California Santa Barbara, United States.

Autosomal-dominant polycystic kidney disease (ADPKD) is a very common genetic disease leading to renal failure. Numerous aberrantly regulated signaling pathways have been identified as promising molecular drug targets for ADPKD therapy. In rodent models, many small-molecule drugs against such targets have proven effective in reducing renal cyst growth. Read More

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Deletion or pharmacological blockade of toll-like receptor 4 (TLR4) confers protection against cyclophosphamide-induced mouse cystitis.

Am J Physiol Renal Physiol 2018 May 2. Epub 2018 May 2.

Pharmacology, State University of Campinas (UNICAMP), Brazil.

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. We investigate the role of toll-like receptor (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)-induced mouse cystitis. Males C57BL/6 (wild-type, WT) and/or TLR4 knockout (TLR4-/-) were treated with an injection of CYP (300 mg/kg, 24 h) or saline (10 ml/kg). Read More

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Different Effects of Global Osteopontin and Macrophage Osteopontin in Glomerular Injury.

Am J Physiol Renal Physiol 2018 May 2. Epub 2018 May 2.

Medicine, University of Colorado Denver, United States.

Osteopontin (OPN) is a pro-and ant-inflammatory molecule that simultaneously attenuates oxidative stress. Both inflammation and oxidative stress play a role in the pathogenesis of glomerulonephritis and in the progression of kidney injury. Importantly, OPN is highly induced in nephritic kidney. Read More

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Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy.

Am J Physiol Renal Physiol 2018 May 2. Epub 2018 May 2.

Zhengzhou University.

Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. Read More

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The impact of preserved Klotho gene expression on anti-oxidative stress activity in healthy kidney.

Am J Physiol Renal Physiol 2018 Apr 25. Epub 2018 Apr 25.

Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University.

Klotho, which was originally identified as an anti-aging gene, forms a complex with fibroblast growth factor 23 (FGF23) receptor in kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho including anti-aging effects such as protection from various cellular stress have been shown, however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and anti-oxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. Read More

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