Targeting a fibrotic bottleneck may provide an OPENING in the treatment of LUTS.
PMID: 30864837 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - March 13, 2019 Category: Physiology Authors: Ricke WA, Bruskewitz RC, Liu TT Tags: Am J Physiol Renal Physiol Source Type: research

Prompt apoptotic response to high glucose in SGLT expressing renal cells.
Abstract It is generally believed that cells that are unable to downregulate glucose transport are particularly vulnerable to hyperglycemia. Yet little is known about the relation between expression of glucose transporters and acute toxic effects of high glucose exposure.Here we have, in an ex vivo study on rat renal cells, compared the apoptotic response to a moderate increase in glucose concentration. We have studied the cell types that commonly are targeted in diabetic kidney disease (DKD): proximal tubule cells (PTC) that express SGLT2, mesangial cells (MC) that express SGLT1, and podocytes that lack SGLT and ...
Source: American Journal of Physiology. Renal Physiology - March 13, 2019 Category: Physiology Authors: Nilsson LM, Zhang L, Bondar A, Svensson D, Wernerson A, Brismar H, Scott L, Aperia A Tags: Am J Physiol Renal Physiol Source Type: research

Urine Podoplanin Heralds the Onset of Ischemia-Reperfusion Injury of the Kidney.
Abstract Ischemia-reperfusion injury represents one of the most common causes of acute kidney injury, a serious and often deadly condition that affects up to 20% of all hospitalized patients in the United States. However, the current standard assay used universally for the diagnosis of acute kidney injury-serum creatinine-does not detect renal damage early in its course. Serendipitously, we found that the immunofluorescent signal of the constitutive podocyte marker podoplanin fades in the glomerulus and intensifies in the tubulointerstitial compartment of the kidney, shortly following ischemia-reperfusion injury i...
Source: American Journal of Physiology. Renal Physiology - March 13, 2019 Category: Physiology Authors: Kasinath V, Yilmam OA, Uehara M, Yonar M, Jiang L, Li X, Qiu W, Eskandari S, Ichimura T, Abdi R Tags: Am J Physiol Renal Physiol Source Type: research

Chronic Kidney Disease and the Gut Microbiome.
Abstract The gut microbiome is composed of a diverse population of bacteria which have beneficial and adverse effects on human health. The microbiome has recently gained attention and is increasingly noted to play a significant role in health and a number of disease states. Increasing urea concentration during chronic kidney disease (CKD) leads to alterations in the intestinal flora that can increase production of gut-derived toxins and alter the intestinal epithelial barrier. These changes can lead to an acceleration of the process of kidney injury. A number of strategies have been proposed to interrupt this path...
Source: American Journal of Physiology. Renal Physiology - March 13, 2019 Category: Physiology Authors: Hobby GP, Karaduta O, Dusio GF, Singh M, Zybailov BL, Arthur JM Tags: Am J Physiol Renal Physiol Source Type: research

Vitamin D receptor activation protects against lipopolysaccharide-induced acute kidney injury through suppression of tubular cell apoptosis.
Abstract Acute kidney injury (AKI) is a common complication of sepsis characterized by a rapid degradation of renal function. The effect of vitamin D on AKI remains poorly understood. Here we showed that vitamin D receptor (VDR) activation protects against lipopolysaccharide (LPS)-induced AKI by blocking renal tubular epithelial cell apoptosis. Mice lacking VDR developed more severe AKI than wild-type (WT) controls following LPS treatment, manifested by marked increases in body weight loss, accumulation of serum BUN and creatinine as well as the magnitude of apoptosis of tubular epithelial cells. In the renal cort...
Source: American Journal of Physiology. Renal Physiology - March 13, 2019 Category: Physiology Authors: Du J, Jiang S, Hu Z, Tang S, Sun Y, He J, Li Z, Yi B, Wang J, Zhang H, Li YC Tags: Am J Physiol Renal Physiol Source Type: research

Sustained, delayed and small increments in glomerular permeability to macromolecules during systemic endothelin-1 infusion mediated via the ETA receptor.
CM Abstract Emerging evidence indicates that endogenous production of endothelin 1 (ET-1), a 21-amino-acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are however currently not known. Here we used size exclusion chromatography to measure glomerular sieving coefficients (θ) for neutral fluorescein isotiocyanate (FITC)-Ficoll (molecular Stokes-Einstein radius: 15-80 Å; MW 70 kDa/400kDa) in anesthetized male Sprague-Dawley rat...
Source: American Journal of Physiology. Renal Physiology - March 13, 2019 Category: Physiology Authors: Dolinina J, Rippe A, Öberg CM Tags: Am J Physiol Renal Physiol Source Type: research

The potential role of myosin motor proteins in mediating the subcellular distribution of NHE3 in the renal proximal tubule.
Abstract Isoform 3 of the Na+/H+ exchanger (NHE3) is responsible for the majority of the reabsorption of NaCl, NaHCO3 and, consequently, water in the renal proximal tubule. As such, this transporter plays an essential role in acid-base balance, extracellular fluid volume homeostasis and determining systemic arterial blood pressure levels. NHE3 activity is modulated by a number of mechanisms, including the redistribution of the transporter between the body of the microvilli (where NHE3 is active) and the base of the microvilli (where NHE3 is less active). Although the physiological, pathophysiological and pharmacol...
Source: American Journal of Physiology. Renal Physiology - March 13, 2019 Category: Physiology Authors: Crajoinas RO, Polidoro JZ, Girardi ACC Tags: Am J Physiol Renal Physiol Source Type: research

Calcium-sensing receptor activation attenuates collagen expression in renal proximal tubular epithelial cells.
Abstract Experimental studies showed that pharmacological activation of calcium-sensing receptor (CaSR) attenuated renal fibrosis in some animal models beyond modification of bone and mineral homeostasis; however, its underlying mechanisms remain largely unknown. Since excessive collagen deposition is the key feature of fibrosis, the present study aimed to examine whether CaSR was involved in the regulation of collagen expression in rats with adenine diet (AD)-induced renal fibrosis and in profibrotic TGF-β1-treated renal proximal tubular epithelial cells (PTECs). The results showed that the CaSR agonist cina...
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Wu M, Feng Y, Ye GX, Han YC, Wang SS, Ni HF, Wang FM, Gao M, Lv LL, Liu BC Tags: Am J Physiol Renal Physiol Source Type: research

Potassium Sparing Effects of Furosemide in Mice on High Potassium Diets.
Abstract On a regular "Western" diet, furosemide induces a kaliuresis and reduction in plasma [K] by inhibiting Na reabsorption in the thick ascending limb of Henle's loop (TAL), enhancing the delivery of Na to the aldosterone sensitive distal nephron. In the aldosterone-sensitive distal nephron, the increased Na delivery stimulates K wasting and due to an exaggerated exchange of epithelial Na channel (ENaC)-mediated Na reabsorption for secreted K. The effects of furosemide are different in mice given a high K, alkaline diet (HK). On HK, the large, Ca-activated K channel (BK), in conjunction with the BK-...
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Wang B, Sansom SC Tags: Am J Physiol Renal Physiol Source Type: research

Loss of miR-17~92 results in dysregulation of Cftr in nephron progenitors.
Abstract We have previously demonstrated that loss of miR-17~92 in nephron progenitors in a mouse modelresults in renal hypodysplasia and chronic kidney disease. Clinically, decreased congenital nephron endowment due to renal hypodysplasia is associated with an increased risk of hypertension and chronic kidney disease, and this is at least partly dependent on the self-renewal of nephron progenitors. Here, we present evidence for a novel molecular mechanism regulating the self-renewal of nephron progenitors and congenital nephron endowment by the highly conserved miR-17~92cluster. Whole transcriptome sequencing rev...
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Phua YL, Chen KH, Hemker SL, Marrone AK, Bodnar AJ, Liu X, Clugston A, Kostka D, Butterworth MB, Ho J Tags: Am J Physiol Renal Physiol Source Type: research

Tubule-vascular feedback in renal autoregulation.
Abstract Afferent arteriole (Af-Art) diameter regulates pressure and flow into the glomerulus, which are the main determinants of the glomerular filtration rate (GFR). Thus, Af-Art resistance is crucial for sodium filtration. Af-Arts play a role as integrative centers, where systemic and local systems interact to determine the final degree of resistance. The tubule of a single nephron contacts an Af-Art of the same nephron at two locations: in the transition of the thick ascending limb to the distal tubule (macula densa) and again in the connecting tubule. These two sites are the anatomical basis of two intrinsic ...
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Romero CA, Carretero OA Tags: Am J Physiol Renal Physiol Source Type: research

TRPV4 deletion protects against hypokalemia during systemic K+ deficiency.
Abstract Tight regulation of K+ balance is fundamental for normal physiology. Reduced dietary K+ intake, which is common in Western diets, often leads to hypokalemia and associated cardiovascular- and kidney-related pathologies. Distal nephron and specifically the collecting duct (CD) is the major site of controlled K+ reabsorption via H+-K+-ATPase in the state of dietary K+ deficiency. We previously demonstrated that TRPV4 Ca2+ channel, abundantly expressed in the CD, contributes to renal K+ handling by promoting flow-induced K+ secretion. Here, we investigated a potential role of TRPV4 in controlling H+-K+-ATPas...
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Tomilin V, Mamenko M, Zaika O, Wingo CS, Pochynyuk OM Tags: Am J Physiol Renal Physiol Source Type: research

Paracellular calcium transport in the proximal tubule and the formation of kidney stones.
Abstract The proximal tubule (PT) is responsible for the majority of calcium reabsorption by the kidney. Most PT calcium transport appears to be passive, although the molecular facilitators have not been well-established. Emerging evidence supports a major role for PT calcium transport in idiopathic hypercalciuria and the development of kidney stones. This review will cover recent developments in our understanding of PT calcium transport and the role of the PT in kidney stone formation. PMID: 30838875 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Curry JN, Yu ASL Tags: Am J Physiol Renal Physiol Source Type: research

Heart-kidney interactions: mechanistic insights from animal models.
Abstract Pathological changes in heart or kidney can instigate the release of a cascade of cardiorenal mediators that promote injury in the other organ. Combined dysfunction of heart and kidney is referred to as cardiorenal syndrome and gained considerable attention. Cardiorenal syndrome has been classified into 5 distinct entities, each with different major pathophysiological changes. Despite the magnitude of the public health problem of cardiorenal syndrome, the underlying mechanisms are incompletely understood and effective intervention is unavailable. Animal models allow us to discover pathogenic molecular cha...
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Liu S Tags: Am J Physiol Renal Physiol Source Type: research

Transcriptome-proteome integration of archival human renal cell carcinoma biopsies enable identification of molecular mechanisms.
Abstract Renal cell cancer is among the most common forms of cancer in humans, with around 35,000 deaths attributed to kidney carcinoma in the European Union (EU) in 2012 alone. Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and the most lethal of all genitourinary cancers. Here we apply omics technologies to archival core biopsies to investigate the biology underlying ccRCC. Knowledge of these underlying processes should be useful for the discovery and/or confirmation of novel therapeutic approaches and ccRCC biomarker development. From partial or full nephrectomies of 11...
Source: American Journal of Physiology. Renal Physiology - March 6, 2019 Category: Physiology Authors: Koch EE, Finne K, Eikrem O, Landolt L, Beisland C, Leh S, Delaleu N, Granly M, Vikse BE, Osman T, Scherer A, Marti HP Tags: Am J Physiol Renal Physiol Source Type: research

The Effects of Aerobic Exercise on Vascular Function in Non-Dialysis Chronic Kidney Disease: A Randomized Controlled Trial.
CONCLUSION: Aerobic exercise improved microvascular function and maintained conduit artery function and should be considered as an adjunct therapy to reduce CVD risk in CKD. PMID: 30810061 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 27, 2019 Category: Physiology Authors: Kirkman DL, Ramick MG, Muth BJ, Stock JM, Pohlig RT, Townsend RT, Edwards DG Tags: Am J Physiol Renal Physiol Source Type: research

Dynamic changes in histone deacetylases following kidney ischemia reperfusion injury are critical for promoting proximal tubule proliferation.
This study demonstrates the need to develop isoform-selective HDAC inhibitors for the treatment of renal hypoperfusion-induced injury. PMID: 30810062 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 27, 2019 Category: Physiology Authors: Hyndman KA, Kasztan M, Mendoza LD, Monteiro-Pai S Tags: Am J Physiol Renal Physiol Source Type: research

Podocyte-specific Expression of Cre Recombinase Promotes Glomerular Basement Membrane Thickening.
Abstract Conditional gene targeting using Cre recombinase has offered a powerful tool to modify gene function precisely in defined cells/tissues and at specific times. However, in mammalian cells, Cre recombinase can be genotoxic. The importance of including Cre-expressing control mice to avoid misinterpretation and to maximize the validity of the experimental results has been increasingly recognized. While studying the role of podocytes in the pathogenesis of glomerular basement membrane (GBM) thickening, we utilized the Cre recombinase driven by the podocyte-specific podocin promoter (NPHS2-Cre) to generate a co...
Source: American Journal of Physiology. Renal Physiology - February 27, 2019 Category: Physiology Authors: Balkawade RS, Chen C, Crowley MR, Crossman DK, Clapp WL, Verlander JW, Marshall CB Tags: Am J Physiol Renal Physiol Source Type: research

A Dual Blocker of Endothelin A/B Receptors Mitigates Hypertension but not Renal Dysfunction in a Rat Model of Chronic Kidney Disease and Sleep Apnea.
Abstract Obstructive sleep apnea (OSA) is characterized by recurrent episodes of pharyngeal collapse during sleep resulting in intermittent hypoxia (IH), and is associated with high incidence of hypertension and accelerated renal failure. In rodents, endothelin-1 (ET-1) contributes to IH-induced hypertension, and ET-1 levels inversely correlate with glomerular filtration rate (GFR) in end-stage chronic kidney disease (CKD) patients. Therefore, we hypothesized that a dual ET receptor antagonist, macitentan (Actelion Pharmaceuticals) will attenuate and reverse hypertension and renal dysfunction in a rat model of com...
Source: American Journal of Physiology. Renal Physiology - February 27, 2019 Category: Physiology Authors: Morales-Loredo H, Jones DT, Barrera A, Mendiola P, Garcia J, Pace CE, Murphy M, Kanagy NL, Gonzalez Bosc LV Tags: Am J Physiol Renal Physiol Source Type: research

Comparison of diabetic nephropathy between male and female eNOS-/- db/db mice.
Abstract Sex is an important biological variable that impacts diverse physiological and pathological processes, including progression of diabetic nephropathy. Diabetic nephropathy is one of the most common complications of diabetes mellitus and is the leading cause of end stage renal disease. eNOS-/- db/db mouse is an appropriate and valuable model to study mechanisms in the development of diabetic nephropathy due to similarities of the features of diabetic kidney disease in this model to those in humans. The aim of the present study was to determine whether there was a sex difference in renal injury in eNOS-/- db...
Source: American Journal of Physiology. Renal Physiology - February 27, 2019 Category: Physiology Authors: Ma Y, Li W, Yazdizadeh Shotorbani P, Dubansky BH, Huang L, Chaudhari S, Wu P, Wang LA, Ryou MG, Zhou Z, Ma R Tags: Am J Physiol Renal Physiol Source Type: research

cGMP Induces Degradation of NKCC2 in the Thick Ascending Limb via the Ubiquitin-Proteasomal System.
Abstract The thick ascending limb of Henle's loop (TAL) reabsorbs sodium chloride via the apical Na+/K+/2Cl- cotransporter (NKCC2). NKCC2 activity is regulated by surface NKCC2 levels. The second messenger cyclic guanosine monophosphate (cGMP) decreases NKCC2 activity by decreasing surface NKCC2 levels. We found that surface NKCC2 undergoes constitutive degradation. Therefore, we hypothesized that cGMP decreases NKCC2 levels by increasing NKCC2 ubiquitination and proteasomal degradation. We measured surface NKCC2 levels by biotinylation of surface proteins, immunoprecipitation of NKCC2 and ubiquitin in TALs. First...
Source: American Journal of Physiology. Renal Physiology - February 27, 2019 Category: Physiology Authors: Ares GR Tags: Am J Physiol Renal Physiol Source Type: research

Arteriovenous Conduits for Hemodialysis: How to Better Modulate the Pathophysiological Vascular Response to Optimize Vascular Access Durability.
Abstract Vascular access is the lifeline for hemodialysis patients. Arteriovenous fistulas (AVFs) are the preferred vascular access but AVF maturation failure remains a significant clinical problem. Currently there are not any effective therapies available to prevent or treat AVF maturation failure. AVF maturation failure frequently results from venous stenosis at the AVF anastomosis, which is secondary to poor outward vascular remodeling and excessive venous intimal hyperplasia that narrows the AVF lumen. Arteriovenous grafts (AVGs) are the next preferred vascular access if an AVF creation is not possible. AVG fa...
Source: American Journal of Physiology. Renal Physiology - February 20, 2019 Category: Physiology Authors: Shiu YT, Rotmans JI, Geelhoed WJ, Pike DB, Lee T Tags: Am J Physiol Renal Physiol Source Type: research

A Model of Uric Acid Transport in the Rat Proximal Tubule.
In conclusion, we have developed the first model of uric acid transport in the rat PT; this model provides a framework to gain greater insight into the numerous solutes and coupling mechanisms that affect the renal handing of uric acid. PMID: 30785349 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 20, 2019 Category: Physiology Authors: Edwards A, Auberson M, Ramakrishnan SK, Bonny O Tags: Am J Physiol Renal Physiol Source Type: research

Angiotensin II and salt-induced decompensation in Balb/CJ mice is aggravated by fluid retention related to low oxidative stress.
CONCLUSION: Balb/CJ mice are more sensitive than C57BL/6J to AngII+Salt in part mediated by lower oxidative stress, which favors fluid and sodium retention. PMID: 30785350 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 20, 2019 Category: Physiology Authors: Jönsson S, Becirovic-Agic M, Isackson H, Tveitarås MK, Skogstrand T, Narfström F, Karlsen TV, Lidén Å, Leh S, Ericsson M, Nilsson SK, Reed RK, Hultström M Tags: Am J Physiol Renal Physiol Source Type: research

Physiological effects of altering oxygenation during kidney normothermic machine perfusion.
Abstract Kidney normothermic machine perfusion (NMP) has historically employed a 95% O2/5% CO2 gas mixture. Using a porcine model of organ retrieval, NMP and reperfusion, we tested the hypothesis that reducing perfusate oxygenation (PPO2) would be detrimental to renal function and cause injury. In a minimal-ischemic-injury (MI) experiment, kidneys sustained 10min of warm ischemia (WI) and 2hr of static cold storage (SCS) before 1hr of NMP with either 95%, 25% or 12% O2 with 5% CO2 and N2 balance. In a clinical-injury (CI) model, kidneys with 10min WI and 17hr SCS underwent 1hr of NMP with the above gas combination...
Source: American Journal of Physiology. Renal Physiology - February 20, 2019 Category: Physiology Authors: Adams TD, Hosgood S, Nicholson ML Tags: Am J Physiol Renal Physiol Source Type: research

Time dependent p53 inhibition determines senescence attenuation and long term outcome after renal ischemia/reperfusion.
In this study we tested the hypothesis that p53 siRNA reduces I/R induced senescence and thereby improves kidney outcome. By comparing the impact of different treatment durations in a mouse model of renal I/R we found that repetitive administration of p53 siRNA during the first 14 days after I/R reduced the senescence load and ameliorated the post-ischemic phenotype. Prolonged application of p53 siRNA over a 26 day period after I/R however, did not provide any additional benefit for senescence reduction, but reversed some of the renoprotective effects of the early treatment. These data suggest a time dependent role of p53 ...
Source: American Journal of Physiology. Renal Physiology - February 20, 2019 Category: Physiology Authors: Baisantry A, Berkenkamp B, Rong S, Bhayadia R, Sörensen-Zender I, Schmitt R, Melk A Tags: Am J Physiol Renal Physiol Source Type: research

IPSE, a parasite-derived host immunomodulatory protein, is a potential therapeutic for hemorrhagic cystitis.
We report that H-IPSEH03, like M-IPSE and H-IPSEH06, activates IgE-bearing basophils in an NFAT reporter assay, indicating activation of the cytokine pathway. Further, H-IPSEH03 attenuates ifosfamide-induced increases in bladder wet weight in an IL-4-dependent fashion. H-IPSEH03 relieves hemorrhagic cystitis-associated allodynia and modulates voiding patterns in mice. Finally, H-IPSEH03 drives increased urothelial cell proliferation suggesting that IPSE induces bladder repair mechanisms. Taken together, H-IPSEH03 may be a potential novel therapeutic to treat hemorrhagic cystitis by basophil activation, attenuation of allod...
Source: American Journal of Physiology. Renal Physiology - February 20, 2019 Category: Physiology Authors: Zee RS, Mbanefo EC, Le LH, Pennington LF, Odegaard J, Jardetzky TS, Alouffi A, Akinwale J, Falcone FH, Hsieh MH Tags: Am J Physiol Renal Physiol Source Type: research

The nephron-arterial network and its interactions.
Abstract Tubuloglomerular feedback and the myogenic mechanism form an ensemble in renal afferent arterioles that regulates single nephron blood flow and glomerular filtration. Each mechanism generates a self-sustained oscillation, the mechanisms interact, and the oscillations synchronize. The synchronization generates a bimodal electrical signal in the arteriolar wall that propagates retrograde to a vascular node where it meets similar electrical signals from other nephrons. Each signal carries information about the time dependent behavior of the regulatory ensemble. The converging signals support synchronization ...
Source: American Journal of Physiology. Renal Physiology - February 13, 2019 Category: Physiology Authors: Marsh DJ, Postnov DD, Sosnovtseva OV, Holstein-Rathlou NH Tags: Am J Physiol Renal Physiol Source Type: research

Novel kidney dissociation protocol and image-based flow cytometry facilitate improved analysis of injured proximal tubules.
We report a new tissue dissociation protocol for kidney with an early fixation step that greatly enhances the yield of single cells. Genetic labeling of the proximal tubule with either the mT/mG "tomato" or the R26Fucci2aR (Fucci) cell cycle reporter mice allows us to follow proximal tubule-specific changes in cell cycle after renal injury. Image-based flow cytometry (FlowSight) enables gating of the cell cycle and concurrent visualization of the cells with brightfield and fluorescence. We used the Fucci mouse in conjunction with FlowSight to identify a discrete polyploid population in proximal tubules after aris...
Source: American Journal of Physiology. Renal Physiology - February 13, 2019 Category: Physiology Authors: Manolopoulou M, Matlock BK, Nlandu Khodo S, Simmons AJ, Lau KS, Phillips-Mignemi M, Ivanova A, Alford CE, Flaherty DK, Gewin LS Tags: Am J Physiol Renal Physiol Source Type: research

Exercise Interventions for Improving Objective Physical Function in End-Stage Kidney Disease Patients on Dialysis: A Systematic Review and Meta-Analysis.
CONCLUSION: From the evidence available, exercise, regardless of modality, improved objective measures of physical function for end stage kidney disease patients undergoing dialysis. It is acknowledged that further well-designed RCTs are required. PMID: 30759022 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 13, 2019 Category: Physiology Authors: Clarkson MJ, Bennett PN, Fraser SF, Warmington SA Tags: Am J Physiol Renal Physiol Source Type: research

Urinary microRNA in Kidney Disease: Utility and Roles.
Abstract MicroRNAs (miRNAs) are small, noncoding single-stranded RNA oligonucleotides that modulate physiological and pathological processes by modulating target gene expression. Many miRNAs display tissue-specific expression patterns, the dysregulation of which has been associated with various disease states, including kidney disease. Mounting evidence implicates miRNAs in various biological processes, such as cell proliferation, differentiation, and cancer. Because miRNAs are relatively stable in tissue and biological fluids, particularly when carried by extracellular vesicles, changes in their levels may reflec...
Source: American Journal of Physiology. Renal Physiology - February 13, 2019 Category: Physiology Authors: Sun IO, Lerman LO Tags: Am J Physiol Renal Physiol Source Type: research

Sex as a Biological Variable in Renal, Metabolic and Cardiovascular Physiology:Eighteen Years of Leadership by the American Physiological Society.
PMID: 30759024 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 13, 2019 Category: Physiology Authors: Ryan MJ, Sullivan JC Tags: Am J Physiol Renal Physiol Source Type: research

Direct and Indirect Inhibition of the Circadian Clock Protein PER1: Effects on ENaC and Blood Pressure.
Abstract Circadian rhythms govern physiological functions and are important for overall health. The molecular circadian clock is comprised of several transcription factors that mediate circadian control of physiological function in part by regulating gene expression in a tissue-specific manner. These connections are well established but the underlying mechanisms are incompletely understood. The overall goal of this study was to examine the connection between the circadian clock protein Per1, ENaC, and BP using a multi-pronged approach. Using global Per1 KO mice on a 129/sv background in combination with a high sal...
Source: American Journal of Physiology. Renal Physiology - February 13, 2019 Category: Physiology Authors: Alli AA, Yu L, Holzworth MR, Richards J, Cheng KY, Lynch IJ, Wingo CS, Gumz ML Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2019 Jan 01;316(1):F219 Authors: PMID: 30624980 [PubMed - in process] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - January 1, 2019 Category: Physiology Tags: Am J Physiol Renal Physiol Source Type: research

Recent Advances in Sex Differences in Kidney Function.
PMID: 30565997 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Layton AT, Sullivan JC Tags: Am J Physiol Renal Physiol Source Type: research

Fructose reabsorption by rat proximal tubules: role of sodium-linked cotransporters and the effect of dietary fructose.
FRUCTOSE REABSORPTION BY RAT PROXIMAL TUBULES: ROLE OF SODIUM-LINKED COTRANSPORTERS AND THE EFFECT OF DIETARY FRUCTOSE. Am J Physiol Renal Physiol. 2018 Dec 19;: Authors: Gonzalez-Vicente A, Cabral PD, Hong NJ, Asirwatham J, Saez F, Garvin JL Abstract Fructose consumption has increased due to widespread use of high-fructose corn syrup by the food industry. Renal proximal tubules are thought to reabsorb fructose. However, fructose reabsorption (Jfructose) by proximal tubules has not yet been directly demonstrated, nor the effects of dietary fructose on Jfructose. This segment express sodium-glucose lin...
Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Gonzalez-Vicente A, Cabral PD, Hong NJ, Asirwatham J, Saez F, Garvin JL Tags: Am J Physiol Renal Physiol Source Type: research

Peroxidasin and Eosinophil Peroxidase, but not Myeloperoxidase, Contribute to Renal Fibrosis in the Murine Unilateral Ureteral Obstruction Model.
Abstract Renal fibrosis is the pathologic hallmark of chronic kidney disease (CKD) and manifests as glomerulosclerosis and tubulointerstitial fibrosis. Reactive oxygen species (ROS) contribute significantly to renal inflammation and fibrosis, but most research has focused on superoxide (O2.-) and hydrogen peroxide (H2O2). The animal heme peroxidases myeloperoxidase (MPO), eosinophil peroxidase (EPX), and peroxidasin (PXDN), uniquely metabolize H2O2 into highly reactive and destructive hypohalous acids, such as hypobromous (HOBr) and hypochlorous (HOCl) acid. But the role of these peroxidases and their downstream h...
Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Colon S, Luan H, Liu Y, Meyer C, Gewin L, Bhave G Tags: Am J Physiol Renal Physiol Source Type: research

Blockade of Enhancer of Zeste Homolog 2 alleviates renal injury associated with hyperuricemia.
In this study, we demonstrated that blockade of EZH2 with 3-DZNeP, a selective EZH2 inhibitor, or silencing of EZH2 with siRNA inhibited uric acid-induced renal fibroblast activation and phosphorylation of Smad3, epidermal growth factor receptor (EGFR) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured renal fibroblasts. Inhibition of EZH2 also suppressed proliferation of renal fibroblasts and epithelial-mesenchymal transition (EMT) of tubular cells. In a mouse model of renal injury induced by hyperuricemia, EZH2 and H3K27me3 expression levels were enhanced, which was coincident with renal dama...
Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Shi Y, Xu L, Tao M, Fang L, Lu J, Gu H, Ma S, Lin T, Wang Y, Bao W, Qiu A, Zhuang S, Liu N Tags: Am J Physiol Renal Physiol Source Type: research

Truncating PKHD1 and PKD2 mutations alter energy metabolism.
Abstract Deficiency in polycystin 1 triggers specific changes in energy metabolism. To determine whether defects in other human cystoproteins have similar effects, we studied extracellular acidification and glucose metabolism in HEK293 cell lines with PKHD1 and PKD2 truncating defects along multiple sites of truncating mutations found in patients with autosomal recessive and dominant polycystic kidney diseases (ARPKD and ADPKD). While the PKHD1 or PKD2 gene mutations or their position had no overall effect on cell proliferation rate in our cell line models, truncating mutations in these genes progressively increas...
Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Chumley P, Zhou J, Mrug S, Chacko BK, Parant JM, Challa AK, Wilson LS, Berryhill TF, Barnes S, Kesterson RA, Bell PD, Darley-Usmar VM, Yoder BK, Mrug M Tags: Am J Physiol Renal Physiol Source Type: research

G-protein coupled receptor 37L1 regulates renal sodium transport and blood pressure.
Abstract GPCRs in the kidney regulate the reabsorption of essential nutrients, ions, and water from the glomerular filtrate. Abnormalities in renal epithelial ion transport play important roles in the pathogenesis of essential hypertension. The orphan G protein-coupled receptor 37L1 (GPR37L1), also known as ETBR-LP2, is expressed in several regions in the brain, but its expression profile and function in peripheral tissues are poorly understood. We found that GPR37L1 mRNA expression is highest in the brain, followed by the stomach, heart, testis, and ovary, with moderate expression in the kidney, pancreas, skeleta...
Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Zheng X, Asico LD, Ma X, Konkalmatt PR Tags: Am J Physiol Renal Physiol Source Type: research

Dietary Oxalate and Kidney Stone Formation.
Abstract Dietary oxalate is plant derived and may be a component of vegetables, nuts, fruits and grains. In normal individuals, approximately half of urinary oxalate is derived from the diet and half from endogenous synthesis. The amount of oxalate excreted in urine plays an important role in calcium oxalate (CaOx) stone formation. Large epidemiologic cohort studies have demonstrated that urinary oxalate excretion is a continuous variable when indexed to stone risk. Thus, those with oxalate excretions greater than 25 mg/day may benefit from a reduction in urinary oxalate output. The 24 hour urine assessment may mi...
Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Mitchell T, Kumar P, Reddy T, Wood KD, Knight J, Assimos DG, Holmes RP Tags: Am J Physiol Renal Physiol Source Type: research

Unravelling reno-protective effects of SGLT2 inhibition in human proximal tubular cells.
Abstract Large clinical trials demonstrated that SGLT2 inhibitors (SGLT2i) slow the progression of kidney function decline in type 2 diabetes. As the underlying molecular mechanisms are largely unknown, we studied the effects of SGLT2i on gene expression in two human proximal tubular (PT) cell lines under normoglycemic conditions, utilizing two SGLT2i, namely empagliflocin and canagliflocin. Genome-wide expression analysis did not reveal substantial differences between these two SGLT2i. Microarray hybridization analysis identified 94 genes that were both upregulated by TGF-ß1 and downregulated by either of t...
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: Pirklbauer M, Schupart R, Fuchs LC, Staudinger P, Corazza U, Sallaberger S, Leierer J, Mayer G, Schramek H Tags: Am J Physiol Renal Physiol Source Type: research

The impact of obesity as an independent risk factor for the development of renal injury: implications from rat models of obesity.
Abstract Diabetes and hypertension are the major causes of chronic kidney disease (CKD). Epidemiological studies within the last few decades have revealed that obesity-associated renal disease is a emerging epidemic and that the increasing prevalence of obesity parallels the increased rate of CKD. This has led to the inclusion of obesity as an independent risk factor for CKD. A major complication when studying the relationship between obesity and renal injury is that cardiovascular and metabolic disorders that may result from obesity including hyperglycemia, hypertension, and dyslipidemia, or the cluster of these ...
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: McPherson KC, Shields CA, Poudel B, Fizer B, Pennington A, Szabo-Johnson A, Thompson WL, Cornelius DC, Williams JM Tags: Am J Physiol Renal Physiol Source Type: research

"I Don't Get No Respect" - The Role of Chloride in Acute Kidney Injury.
"I Don't Get No Respect" - The Role of Chloride in Acute Kidney Injury. Am J Physiol Renal Physiol. 2018 Dec 12;: Authors: Rein JL, Coca SG Abstract Acute kidney injury (AKI) is a major public health problem that complicates 10-40% of hospital admissions. Importantly, AKI is independently associated with increased risk of progression to chronic kidney disease, end stage renal disease, cardiovascular events, and increased risk of in-hospital and long-term mortality. The chloride content of intravenous fluid has garnered much attention over the last decade, and its association with excess use ...
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: Rein JL, Coca SG Tags: Am J Physiol Renal Physiol Source Type: research

Myo-inositol oxygenase accentuates renal tubular injury initiated by endoplasmic reticulum (er) stress.
MYO-INOSITOL OXYGENASE ACCENTUATES RENAL TUBULAR INJURY INITIATED BY ENDOPLASMIC RETICULUM (ER) STRESS. Am J Physiol Renal Physiol. 2018 Dec 12;: Authors: Tominaga T, Sharma I, Fujita Y, Doi T, Wallner AK, Kanwar YS Abstract Besides oxidant stress, ER stress has been implicated in the pathogenesis of various metabolic disorders affecting kidney. These two forms of stresses are not mutually exclusive to each other and may operate by a feedback loop in worsening the cellular injury. To attest to this contention studies were performed to assess if in such a setting there is worsening of tubulo-interstiti...
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: Tominaga T, Sharma I, Fujita Y, Doi T, Wallner AK, Kanwar YS Tags: Am J Physiol Renal Physiol Source Type: research

Nudel involvement in the high glucose-induced epithelial-mesenchymal transition of tubular epithelial cells.
Abstract Nudel is a newly discovered factor related to cell migration. The tubular epithelial-mesenchymal transition (EMT) includes four steps: the loss of the adhesive properties of epithelial cells, the acquisition of a mesenchymal cell phenotype, the destruction of the tubular basal membrane and the migration into the renal interstitium. The purpose of this study was to investigate the role of Nudel in the high glucose-induced EMT of tubular epithelial cells. Human renal proximal tubular epithelial cells (HKCs) were treated with Nudel shRNA to clarify the role and mechanism of Nudel in tubular EMT induced by hi...
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: Zhang W, Xing LL, Xu L, Jin X, Du Y, Feng X, Liu SX, Liu Q Tags: Am J Physiol Renal Physiol Source Type: research

Periostin Induces Kidney Fibrosis after Acute Kidney Injury via the p38 MAPK Pathway.
In conclusion, periostin promotes kidney fibrosis via the p38 MAPK pathway following acute kidney injury triggered by a hypoxic or ischemic insult. Periostin ablation may protect against CKD progression. PMID: 30539653 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: An JN, Yang SH, Kim YC, Hwang JH, Park JY, Kim DK, Kim JH, Kim DW, Hur DG, Oh YK, Lim CS, Kim YS, Lee JP Tags: Am J Physiol Renal Physiol Source Type: research

Lack of urea transporters, UT-A1 and UT-A3, increases nitric oxide accumulation to dampen medullary sodium reabsorption through ENaC.
Abstract While the role of urea in urine concentration is known, the effect of urea handling by the urea transporters, UT-A1 and UT-A3, on sodium balance remains elusive. Serum and urinary sodium concentration is similar between wild-type mice (WT) and UT-A3 null (UT-A3 KO) mice; however, mice lacking both UT-A1 and UT-A3 (UT-A1/A3 KO) have significantly lower serum sodium and higher urinary sodium. Protein expression of renal sodium transporters is unchanged among all three genotypes. WT, UT-A3 KO and UT-A1/A3 KO acutely respond to hydrochlorothiazide and furosemide; however, UT-A1/A3 KO fail to show a diuretic o...
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: Rogers RT, Sun MA, Yue Q, Bao HF, Sands JM, Blount MA, Eaton DC Tags: Am J Physiol Renal Physiol Source Type: research

Prohibitin 2-mediated mitophagy attenuates renal tubular epithelial cells injury by regulating mitochondrial dysfunction and NLRP3 inflammasome activation.
In this study, we confirmed that autophagy is activated in tubular epithelial cells treated with angiotensin II, and that inhibition of autophagy results in tubular cell injury. Strikingly, PHB2 knockdown reduced the level of mitophagy and augmented cell death, while overexpression of PHB2 provided protection against NLRP3-induced inflammatory pathways through amelioration of mitochondrial dysfunction. Our research is the first to experimentally demonstrate the role of PHB2 in kidney disease, and thereby, to provide a better understanding of how autophagy modulates inflammation in renal tubules. These data highlight PHB2 a...
Source: American Journal of Physiology. Renal Physiology - December 12, 2018 Category: Physiology Authors: Xu Y, Wang J, Xu W, Ding F, Ding W Tags: Am J Physiol Renal Physiol Source Type: research

Cloning, function, and localization of human, canine and Drosophila Zip10 (Slc39a10), a Zn2+ transporter.
The objective of this study was to show ZIP10 homologs transport Zn2+, as well as ZIP10 kidney localization across species.. We cloned ZIP10 from dog, human, and Drosophila ( CG10006), tested clones for Zn2+ uptake in Xenopus oocytes, and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule but also the collecting duct system. These Z...
Source: American Journal of Physiology. Renal Physiology - December 6, 2018 Category: Physiology Authors: Landry GM, Furrow E, Holmes HL, Hirata T, Kato A, Williams P, Strohmaier K, Gallo CJR, Chang MH, Pandey MK, Jiang H, Bansal A, Franz MC, Montalbetti N, Alexander MP, Cabrero P, Dow JAT, DeGrado TR, Romero MF Tags: Am J Physiol Renal Physiol Source Type: research