E3 ligase MDM2 mediates urea transporter A1 ubiquitination under either constitutive or stimulatory conditions.
In conclusion, MDM2 binds with UT-A1 and mediates its ubiquitination and degradation in an AP50 dependent manner, and their binding capacity is strengthened under FSK and diabetic milieu. PMID: 31509007 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - September 11, 2019 Category: Physiology Authors: Su H, Ye C, Sands JM, Zhang C Tags: Am J Physiol Renal Physiol Source Type: research

Activities of Calcium-Related Ion Channels during the Formation of Kidney Stones in an Infection-Induced Urolithiasis Rat Model.
In this study, we hypothesized another possible method of bacteria contributing to the formation of calcium oxalate (CaOx) that accounts for the biggest part of the kidney stone. Bacteria may play important roles by influencing renal calcium-related ion channel activities, resulting in chronic inflammation of the kidney along with the rapid aggregation of stones. We examined the correlation among infection-promoted CaOx kidney stones and alterations in calcium-related ion channels in an animal model with experimentally induced Proteus mirabilis and foreign-body infection. After infecting the bladder for 7 days, the data de...
Source: American Journal of Physiology. Renal Physiology - September 11, 2019 Category: Physiology Authors: Cherng JH, Hsu YJ, Liu CC, Tang SH, Sartika D, Chang SJ, Fan GY, Wu ST, Meng E Tags: Am J Physiol Renal Physiol Source Type: research

Capillary rarefaction is more closely associated with CKD progression after cisplatin, rhabdomyolysis, and ischemia reperfusion-induced AKI than renal fibrosis.
Abstract Acute kidney injury (AKI) is a strong independent predictor of mortality, and often results in incomplete recovery of renal function, leading to progressive chronic kidney disease (CKD). Many clinical trials have been conducted based on promising preclinical data, but no therapeutic interventions have been shown to improve long-term outcomes after AKI. This is partly due to the failure of preclinical studies to accurately model clinically relevant injury and long-term outcomes on CKD progression. Here, we evaluated the long-term effects of AKI on CKD progression in three animal models reflecting diverse e...
Source: American Journal of Physiology. Renal Physiology - September 11, 2019 Category: Physiology Authors: Menshikh A, Scarfe L, Delgado R, Finney C, Zhu Y, Yang H, de Caestecker MP Tags: Am J Physiol Renal Physiol Source Type: research

Regulation of mitochondria function by natriuretic peptides.
Abstract Natriuretic peptides (NP) are well known to promote renal sodium excretion, opposing the effects caused by the renin-angiotensin-aldosterone system. Thus, NPs serve as a key component in the maintenance of the blood pressure, influencing fluid retention capabilities via osmoregulation. Recently, NPs have been shown to affect lipolysis, and enhance lipid oxidation and mitochondrial respiration. Here we provided an overview of current knowledge about the relationship between NPs and mitochondria-mediated processes such as reactive oxygen species production, calcium signaling, and apoptosis. Establishing a c...
Source: American Journal of Physiology. Renal Physiology - September 11, 2019 Category: Physiology Authors: Domondon M, Nikiforova AB, DeLeon-Pennell KY, Ilatovskaya DV Tags: Am J Physiol Renal Physiol Source Type: research

In utero exposure to maternal diabetes impairs nephron progenitor differentiation.
Abstract The incidence of diabetes mellitus has significantly increased among women of childbearing age and it has been shown that prenatal exposure to maternal diabetes increases the risk of associated congenital anomalies of the kidney. Congenital anomalies of the kidney are amongst the leading causes of chronic kidney disease in children. To better understand the effect of maternal diabetes on kidney development, we analyzed wildtype offspring (DM_Exp) of diabetic Ins2+/C96Ymice (Akitamice). DM_Exp mice at postnatal day 34 (P34) have a reduction of approximately 20% in the total nephron number compared to contr...
Source: American Journal of Physiology. Renal Physiology - September 11, 2019 Category: Physiology Authors: Cerqueira DM, Hemker SL, Bodnar AJ, Ortiz DM, Oladipupo FO, Mukherjee E, Gong Z, Appolonia C, Muzumdar RH, Sims-Lucas S, Ho J Tags: Am J Physiol Renal Physiol Source Type: research

Complement C1r serine protease contributes to kidney fibrosis.
We reported that complement activation precedes the development of kidney fibrosis, however, little is known about the cellular mechanisms involved in this transition. We hypothesize that increased expression of C1 complex protease C1r, the initiator of complement activation, contributes to tubulointerstitial fibrosis, and tested this idea in mice with global deletion of C1r. Although the expression of C1r in untreated wild type (WT) mice is higher in liver when compared to kidney tissue, administration of folic acid (FA) led to upregulation of C1r mRNA and protein levels only in kidney tissue. Immunohistochemistry and in ...
Source: American Journal of Physiology. Renal Physiology - September 11, 2019 Category: Physiology Authors: Xavier S, Sahu RK, Bontha SV, Mass V, Taylor RP, Megyesi J, Thielens NM, Portilla D Tags: Am J Physiol Renal Physiol Source Type: research

A peek into Epac physiology in the kidney.
Abstract Cyclic adenosine monophosphate (cAMP) is a critical second messenger of numerous endocrine signals affecting water-electrolyte transport in the renal tubule. Exchange protein directly activated by cAMP (Epac) is a relatively recently discovered downstream effector of cAMP having the same affinity to the second messenger as the protein kinase A (PKA), the classical cAMP target. Two Epac isoforms, Epac1 and Epac2 are abundantly expressed in the renal epithelium, where they are thought to regulate water and electrolyte transport particularly in the proximal tubule and the collecting duct. Recent characteriza...
Source: American Journal of Physiology. Renal Physiology - September 11, 2019 Category: Physiology Authors: Tomilin VN, Pochynyuk OM Tags: Am J Physiol Renal Physiol Source Type: research

Extracorporeal Resuscitation with Carbon Monoxide Improves Renal Function by Targeting Inflammatory Pathways in Cardiac Arrest in Pigs.
Abstract BACKGROUND: Deleterious consequences like acute kidney injury frequently occur upon successful resuscitation from cardiac arrest. Extracorporeal life support is increasingly used to overcome high cardiac arrest mortality. Carbon monoxide (CO) is an endogenous gasotransmitter, capable of reducing renal injury. In our study, we hypothesize that addition of CO to extracorporeal resuscitation hampers severity of renal injury in a porcine model of cardiac arrest. METHODS: Hypoxic cardiac arrest was induced in pigs. Animals were resuscitated using a conventional (CPR), an extracorporeal (E-CPR) or a CO-ass...
Source: American Journal of Physiology. Renal Physiology - September 4, 2019 Category: Physiology Authors: Wollborn J, Schlueter B, Steiger C, Hermann C, Wunder C, Schmidt J, Diel P, Meinel L, Buerkle H, Goebel U, Schick MA Tags: Am J Physiol Renal Physiol Source Type: research

Involvement of high-mobility group box 1 in the pathogenesis of severe hemolytic uremic syndrome in a murine model.
Abstract Typical hemolytic uremic syndrome is caused by the Shiga toxin (Stx2) and lipopolysaccharide (LPS) of Escherichia coli and leads to acute kidney injury. The role of innate immunity in this pathogenesis is unclear. We analyzed the role of high-mobility group box 1 (HMGB1) at the onset of disease in a murine model. C57BL/6 mice were intraperitoneally administered with saline (Group A); anti-HMGB1 monoclonal antibody (Group B); Stx2 and LPS, to elicit severe disease (Group C); or Stx2, LPS, and anti-HMGB1 antibody (Group D). While all Group C mice died by day 5 of the experiment, all Group D mice survived. A...
Source: American Journal of Physiology. Renal Physiology - September 4, 2019 Category: Physiology Authors: Maeda R, Kawasaki Y, Kume Y, Go H, Suyama K, Hosoya M Tags: Am J Physiol Renal Physiol Source Type: research

Analysis of the critical determinants of renal medullary oxygenation.
Abstract We previously developed a three-dimensional computational model of oxygen transport in the renal medulla. In the present study, we employed this model to quantify the sensitivity of renal medullary oxygenation to four of its major known determinants: medullary blood flow (MBF), medullary oxygen consumption rate (VO2,M), hemoglobin concentration in the blood (Hb), and renal perfusion pressure (RPP). We also examined medullary oxygenation under special conditions of hydropenia, extracellular fluid volume expansion by infusion of isotonic saline, and hemodilution during cardiopulmonary bypass (CPB). Under ba...
Source: American Journal of Physiology. Renal Physiology - September 4, 2019 Category: Physiology Authors: Lee CJ, Gardiner BS, Evans RG, Smith DW Tags: Am J Physiol Renal Physiol Source Type: research

Reduced skeletal muscle expression of mitochondrial derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease.
n F Abstract Reduced skeletal muscle expression of mitochondrial derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease Advanced chronic kidney disease (CKD) is characterized by a premature ageing phenotype of multifactorial origin. Mitochondrial dysfunction is prevalent in CKD and has been proposed as a major contributor to poor muscle function. Although mitochondrial derived peptides (MDPs) humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis and glucose control, the implications of MDP in CKD are unknown. We investigated ...
Source: American Journal of Physiology. Renal Physiology - August 21, 2019 Category: Physiology Authors: Liu C, Gidlund EK, Witasp A, Qureshi AR, Söderberg M, Thorell A, Nader GA, Barany P, Stenvinkel P, von Walden F Tags: Am J Physiol Renal Physiol Source Type: research

Antagonism of major histocompatibility complex class II invariant chain peptide during chronic lipopolysaccharide treatment rescues autoregulatory behavior.
Abstract Toll-like receptor 4 (TLR4) activation contributes to vascular dysfunction in pathological conditions such as hypertension and diabetes, but the role of chronic TLR4 activation on renal autoregulatory behavior is unknown. We hypothesized that sub-clinical TLR4 stimulation with low-dose lipopolysaccharide (LPS) infusion increases TLR4 activation and blunts renal autoregulatory behavior. We assessed afferent arteriole (AA) autoregulatory behavior in male Sprague Dawley rats after prolonged LPS (0.1mg/kg/day; s.q.) infusion via osmotic minipump for 8 or 14 days. Some rats also received daily co-treatment wit...
Source: American Journal of Physiology. Renal Physiology - August 21, 2019 Category: Physiology Authors: Van Beusecum JP, Zhang S, Beltran E, Cook AK, Tobin RP, Newell-Rogers MK, Inscho EW Tags: Am J Physiol Renal Physiol Source Type: research

Rho-Kinase Inhibitors Reduce Voltage-dependent Calcium Channel Signaling in Aortic and Renal Microvascular Smooth Muscle Cells.
Abstract Voltage-dependent L-type calcium channels (L-VDCCs) and the rhoA/rho-kinase pathway are two predominant intracellular signaling pathways that regulate renal microvascular reactivity. Traditionally, these two pathways have been thought to act independently; however, recent evidence suggests these pathways could be convergent. We hypothesized that rho-kinase inhibitors can influence L-VDCC signaling. The effects of rho-kinase inhibitors Y-27632 or RKI-1447 on KCl-depolarization or the L-VDCC agonist, Bay K8644 were assessed in afferent arterioles using the in vitro blood-perfused rat juxtamedullary nephron ...
Source: American Journal of Physiology. Renal Physiology - August 21, 2019 Category: Physiology Authors: Guan Z, Baty JJ, Zhang S, Remedies CE, Inscho EW Tags: Am J Physiol Renal Physiol Source Type: research

Kidney Dopamine D1-like Receptors and Angiotensin 1-7 Interaction Inhibits Renal Sodium Transporters.
This study aims to investigate the hypothesis that Ang 1-7 could regulate sodium homeostasis by modulating renal dopamine system. Sprague Dawley rats were infused with saline alone (vehicle) or saline with Ang 1-7, Ang 1-7 antagonist A-779, DR agonist SKF38393, and antagonist SCH23390. Infusion of Ang 1-7 caused significant natriuresis and diuresis when compared to saline alone. Both natriuresis and diuresis were blocked by A-779 and SCH23390. SKF38393 caused a significant, SCH23390 sensitive, natriuresis and diuresis and A-779 had no effect on SKF38393 response. Concomitant infusion of Ang 1-7 and SKF38393 did not show a ...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Banday AA, Diaz Diaz A, Lokhandwala M Tags: Am J Physiol Renal Physiol Source Type: research

Urinary extracellular vesicles: mothership connection.
PMID: 31411070 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Blijdorp CJ, Hoorn EJ Tags: Am J Physiol Renal Physiol Source Type: research

The protective effect of klotho against contrast-associated acute kidney injury via the anti-oxidative effect.
This study showed that klotho in the proximal tubular cells can protect against CA-AKI via the anti-oxidative effect. PMID: 31411071 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Oh HJ, Oh H, Nam BY, You JS, Ryu DR, Kang SW, Chung YE Tags: Am J Physiol Renal Physiol Source Type: research

Timing of Sacral Neurostimulation is Important for Increasing Bladder Capacity in the Anesthetized Rat.
Abstract We assessed the effects of limited application of SNS during bladder filling on bladder capacity utilizing our previously published sacral neurostimulation (SNS) model in rats. Female Sprague-Dawley rats (n=24) were urethane-anesthetized (s.c. 1.2 g/kg) and implanted with jugular venous and transvesical bladder catheters. The L6/S1 nerve trunks were isolated bilaterally and two electrodes were placed on each exposed nerve. True bladder capacity (TBC) was determined using stable single-fill cystometrograms. In the first series of experiments, SNS was applied at the onset of bladder filling for 25%, 50%, 75...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Potts BA, Degoski DJ, Brooks JM, Peterson AC, Nelson DE, Brink TS, Fraser MO Tags: Am J Physiol Renal Physiol Source Type: research

Pathogenic role of innate immunity in a model of chronic NO inhibition associated with salt overload.
ujihara CK Abstract Nitric oxide inhibition with Nw-nitroarginine-methylester (L-NAME) along with salt overload leads to hypertension, albuminuria, glomerulosclerosis, glomerular ischemia and interstitial fibrosis, characterizing a chronic kidney disease (CKD) model. Previous findings of this laboratory and elsewhere suggest that activation of at least two pathways of innate immunity, TLR4/NF-κB and NLRP3 inflammasome/IL-1β, occurs in several experimental models of CKD, and that progression of renal injury can be slowed with inhibition of these pathways. In the present study, we investigated whether act...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Zambom FFF, Oliveira KC, Foresto-Neto O, Faustino VD, Ávila VF, Albino AH, Arias SCA, Volpini RA, Malheiros DMAC, Saraiva Câmara NO, Zatz R, Fujihara CK Tags: Am J Physiol Renal Physiol Source Type: research

Long-term outcomes in mouse models of ischemia-reperfusion induced acute kidney injury.
Abstract Severe acute kidney injury (AKI) has a high mortality and is a risk factor for progressive chronic kidney disease (CKD). None of the potential therapies that have been identified in preclinical studies have successfully improved clinical outcomes. This failure is partly because animal models rarely reflect the complexity of human disease: most preclinical studies are short-term, and are commonly performed in healthy, young, male mice. Therapies that are effective in preclinical models that share common clinical features seen in patients with AKI including genetic diversity, different sexes and co-morbidit...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Scarfe L, Menshikh A, Newton E, Zhu Y, Delgado R, Finney C, de Caestecker MP Tags: Am J Physiol Renal Physiol Source Type: research

Obesity Causes Renal Mitochondrial Dysfunction and Energy Imbalance and Accelerates Chronic Kidney Disease in Mice.
Abstract Obesity, as well as the metabolic syndrome, are well known risk factors for chronic kidney disease (CKD), but less is known about the mechanism(s) by which metabolic syndrome might accelerate kidney disease. We hypothesized that metabolic syndrome should accelerate the development of kidney disease and that it might be associated with alterations in energy metabolism.We studied the pound mouse (which develops early metabolic syndrome due to a leptin receptor deletion) and wild type littermates and compared the level of renal injury and muscle wasting following equivalent injury with oral adenine. Renal fu...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Andres-Hernando A, Lanaspa MA, Kuwabara M, Orlicky DJ, Cicerchi C, Bales E, Garcia GE, Roncal-Jimenez CA, Sato Y, Johnson RJ Tags: Am J Physiol Renal Physiol Source Type: research

LC-MS-based metabolomics analysis to identify meprin β-associated changes in kidney tissue from mice with STZ-induced type 1 diabetes and diabetic kidney injury.
LC-MS-based metabolomics analysis to identify meprin β-associated changes in kidney tissue from mice with STZ-induced type 1 diabetes and diabetic kidney injury. Am J Physiol Renal Physiol. 2019 Aug 14;: Authors: Gooding J, Cao L, Ahmed F, Mwiza JM, Fernander M, Whitaker C, Acuff Z, McRitchie S, Sumner S, Ongeri EM Abstract Meprin metalloproteases have been implicated in the pathophysiology of diabetic kidney disease (DKD). SNPs in the meprin β gene associated with DKD in the Pima Indians, a Native American ethnic group with extremely high prevalence of DKD. In diabetic African American men,...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Gooding J, Cao L, Ahmed F, Mwiza JM, Fernander M, Whitaker C, Acuff Z, McRitchie S, Sumner S, Ongeri EM Tags: Am J Physiol Renal Physiol Source Type: research

Multiple doses of stem cells maintain urethral function in a model of neuromuscular injury resulting in stress urinary incontinence.
MULTIPLE DOSES OF STEM CELLS MAINTAIN URETHRAL FUNCTION IN A MODEL OF NEUROMUSCULAR INJURY RESULTING IN STRESS URINARY INCONTINENCE. Am J Physiol Renal Physiol. 2019 Aug 14;: Authors: Janssen K, Lin DL, Hanzlicek B, Deng K, Balog BM, van der Vaart CH, Damaser MS Abstract Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a caesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of this...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Janssen K, Lin DL, Hanzlicek B, Deng K, Balog BM, van der Vaart CH, Damaser MS Tags: Am J Physiol Renal Physiol Source Type: research

Sonic hedgehog selectively promotes lymphangiogenesis after kidney injury through noncanonical pathway.
Abstract Kidney fibrosis is associated with an increased lymphangiogenesis, characterized by the formation and expansion of new lymphatic vessels. However, the trigger and underlying mechanism responsible for the growth of lymphatic vessels in diseased kidney remain poorly defined. Here we report that tubule-derived sonic hedgehog (Shh) ligand is a novel lymphangiogenic factor that plays a crucial role in mediating lymphatic endothelial cell proliferation and expansion. Shh was induced in renal tubular epithelium in various models of fibrotic CKD, and this was accompanied by an expansion of lymphatic vessels in ad...
Source: American Journal of Physiology. Renal Physiology - August 14, 2019 Category: Physiology Authors: Zhuo H, Zhou D, Wang Y, Mo H, Yu Y, Liu Y Tags: Am J Physiol Renal Physiol Source Type: research

The increase of core temperature affected the progression of kidney injury by repeated heat stress exposure.
Abstract BACKGROUND: An epidemic of chronic kidney disease of unknown etiology (Mesoamerican Nephropathy) has emerged in hot regions of Central America. We have demonstrated that dehydration associated with recurrent heat exposure causes chronic kidney disease in animal models. However, the independent influence of the core body temperature to kidney injury has not been explored. Here we tested the hypothesis that kidney injury could be accelerated by increasing body temperature independent of external temperature. METHODS: Wild type mice were exposed heat (39.5°C, 30 min, 2 times daily) with or without t...
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Sato Y, Roncal-Jimenez CA, Andres-Hernando A, Jensen T, Tolan DR, Sanchez-Lozada LG, Newman LS, Butler-Dawson J, Sorensen C, Glaser J, Miyazaki M, Diaz HF, Ishimoto T, Kosugi T, Maruyama S, Garcia GE, Lanaspa MA, Johnson RJ Tags: Am J Physiol Renal Physiol Source Type: research

Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.
In conclusion, our data demonstrate that PTHrP is excreted in the rat urine, and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker. PMID: 31390230 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Ortega A, Olea-Herrero N, Arenas MI, Vélez-Vélez E, Moreno-Gómez-Toledano R, Muñoz-Moreno C, Lázaro A, Esbrit P, Tejedor A, Bosch RJ Tags: Am J Physiol Renal Physiol Source Type: research

Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology: Functional Assessment.
Abstract Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of Lower Urinary Tract Symptoms (LUTS). Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomical, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multi-parameter "baseline" of voiding fun...
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Ruetten H, Wegner KA, Zhang HL, Wang P, Sandhu JK, Sandhu SK, Mueller B, Wang Z, Macoska J, Peterson RE, Bjorling DE, Ricke WA, Marker PC, Vezina CM Tags: Am J Physiol Renal Physiol Source Type: research

Sex-Difference In Kidney Electrolyte Transport II: Impact of K intake on Thiazide-Sensitive Cation Excretion in Male and Female Mice.
Abstract We studied sex differences in response to high K (HK) intake on thiazide-sensitive cation (Na+and K+) excretion in WT and AT1aKO mice. Renal clearance experiments were performed to examine NCC activity on mice fed with control (CK) and high-K (HK, (5% KCl, 7 days) diets. The hydrochlorothiazide (HCTZ)-induced changes in urine volume (UV), glomerular filtration rate (GFR), absolute (ENa, EK) and fractional (FENa, FEK) excretion were compared. HK-induced changes in NCC, Na/H-exchanger isoform 3 (NHE3), and ENaC expression were examined by Western blotting. In WT animals, under CK-diet, HCTZ-induced cation e...
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Li J, Xu S, Yang L, Yang J, Wang CJ, Weinstein AM, Palmer LG, Wang T Tags: Am J Physiol Renal Physiol Source Type: research

Does glucagon-like peptide-1 (GLP-1) induce diuresis and natriuresis by modulating afferent renal nerve activity?
Abstract Glucagon-like peptide-1 (GLP-1), incretin hormone, has diuretic and natriuretic effects. The present study was designed to explore the possible underlying mechanisms for the diuretic and natriuretic effects of GLP-1 via renal nerves in rats. Immunohistochemistry revealed that GLP-1 receptors were avidly expressed in the pelvic wall being adjacent to afferent renal nerves immunoreactive to calcitonin-gene-related peptide, which is the dominant neurotransmitters for renal afferents. GLP-1 (3 μM) infused into left renal pelvis increased ipsilateral afferent renal nerve activity (110.0 ± 15.6% of ba...
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Katsurada K, Nandi SS, Sharma NM, Zheng H, Liu X, Patel KP Tags: Am J Physiol Renal Physiol Source Type: research

Differences in Acidosis-Stimulated Renal Ammonia Metabolism in the Male and Female Kidney.
Abstract Renal ammonia excretion is a critical component of acid-base homeostasis and changes in ammonia excretion are the predominant component of increased net acid excretion in response to metabolic acidosis. We recently reported substantial sex-dependent differences in basal ammonia metabolism that correlate with sex-dependent differences in renal structure and expression of key proteins involved in ammonia metabolism. The purpose of the current study was to investigate the effect of sex on the renal ammonia response to an exogenous acid load. We studied 4-month old C57BL/6 mice. Ammonia excretion, which was l...
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Harris AN, Lee HW, Fang L, Verlander JW, Weiner ID Tags: Am J Physiol Renal Physiol Source Type: research

Diabetes aggravates renal ischemia reperfusion injury by repressing mitochondrial function and PINK1/Parkin-mediated mitophagy.
CONCLUSION: Our results, for the first time, indicated that diabetes could aggravate I/R injury by repressing mitochondrial function and PINK1/Parkin-mediated mitophagy in vivo and in vitro. PMID: 31390235 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Yang YY, Gong DJ, Zhang J, Liu X, Wang L Tags: Am J Physiol Renal Physiol Source Type: research

Sphingosine-1-phosphate signaling in blood pressure regulation.
Abstract Sphingolipids were originally believed to play a role only as a backbone of mammalian cell membranes. However, sphingolipid metabolites, especially sphingosine-1-phosphate (S1P), are now recognized as new bioactive signaling molecules that are critically involved in numerous cellular functions of multiple systems including the immune system, central nervous system, and cardiovascular system. S1P research has accelerated in the last decade as new therapeutic drugs have emerged that target the S1P signaling axis to treat diseases of the immune and central nervous systems. There is limited knowledge of the s...
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Intapad S Tags: Am J Physiol Renal Physiol Source Type: research

Circadian variation in the release of small extracellular vesicles can be normalized by vesicle number or TSG101.
Abstract Numerous candidate biomarkers in urine extracellular vesicles (EVs) have been described for kidney diseases but none are yet in clinical use, possibly due to a lack of proper normalization. Proper normalization corrects for normal biological variation in urine flow rate or concentration, which can vary by over an order of magnitude. Here, we observed inter- and intra-animal variation in urine excretion rates of small EVs (
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Koritzinsky EH, Street JM, Chari RR, Glispie DM, Bellomo TR, Aponte AM, Star RA, Yuen PST Tags: Am J Physiol Renal Physiol Source Type: research

Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy.
We examined the effects of empagliflozin, a selective inhibitor of sodium glucose cotransporter-2 (SGLT-2) on mitochondrial quality control and autophagy in renal tubular cells in a diabetic environment in vivo and in vitro. Human renal proximal epithelial cells (hRPTCs) were incubated in high-glucose conditions. Diabetes was induced with streptozotocin (STZ) in male C57/BL6J mice. Improvements in mitochondrial biogenesis and balanced fusion/fission protein expression were noted in hRPTCs after treatment with empagliflozin in high-glucose media. Empagliflozin also increased autophagic activities in renal tubular cells unde...
Source: American Journal of Physiology. Renal Physiology - August 7, 2019 Category: Physiology Authors: Lee YH, Kim SH, Kang JM, Heo JH, Kim DJ, Park SH, Sung M, Kim J, Oh J, Yang DH, Lee SH, Lee SY Tags: Am J Physiol Renal Physiol Source Type: research

Extracellular vesicles as novel diagnostic and research tool for patients with HTN and Kidney disease.
Abstract Hypertension (HTN) affects one in three adults in the US and is a major risk factor for cardiovascular disease (CVD) and kidney failure. There is emerging evidence that more intense blood pressure (BP) lowering reduces mortality in patients with kidney disease who are at risk of CVD and progression to end-stage renal disease. However, the ideal blood pressure threshold for patients with kidney disease remain a question of debate and controversy. Novel tools to more precisely diagnose HTN, tailor treatment and predict risk of end organ damage such as kidney disease are needed. Analysis of circulating and u...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Erdbruegger U, Le TH Tags: Am J Physiol Renal Physiol Source Type: research

Loss of Primary Cilia Increases Polycystin-2 and TRPV4 and Appearance of a Non-selective Cation Channel in Mouse Cortical Collecting Duct.
Abstract Flow related bending of cilia results in calcium influx through a polycystin-1 and polycystin-2 complex both of which are members of the TRP family (TRPP1 and TRPP2, respectively). Deletion of this complex as well as cilia result in polycystic kidney disease. The calcium influx pathway was previously characterized in immortalized collecting duct cells without cilia and was found to be a 23 pS channel that was multimere of TRPP2 and TRPV4. The purpose of this study was to determine if this TRPP2 and TRPV4 multimere exists in vivo. Apical channel activity was measured using the patch clamp technique, from i...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Saigusa T, Yue Q, Bunni MA, Darwin Bell P, Eaton DC Tags: Am J Physiol Renal Physiol Source Type: research

Urine Complement Activation Fragments are Increased in Patients with Kidney Injury After Cardiac Surgery.
Abstract Experiments in mouse models have shown that the complement cascade is activated within the kidney after ischemia/reperfusion, and that complement activation contributes to tubular injury in this setting. Less is known, however, about complement activation in human kidneys after ischemia, or whether complement activation in the tubulointerstitium can be detected by measurement of complement fragments in the urine. We hypothesized that urine biomarkers of complement activation would rapidly increase in patients who develop ischemic acute kidney injury, signaling complement activation within the kidney. We c...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Laskowski J, Thiessen Philbrook H, Parikh CR, Thurman JM Tags: Am J Physiol Renal Physiol Source Type: research

Kinetic Basis of Metformin-MPP Interactions with the Organic Cation Transporter OCT2.
Abstract The organic cation transporter OCT2 clears the blood of cationic drugs. Efforts to understand OCT2 selectivity as a means to predict the potential of new molecular entities (NMEs) to produce unwanted drug-drug interactions typically assess the influence of the NME on inhibition of transport. However, identity of the substrate used to assess transport activity can influence the quantitative profile of inhibition. Metformin and 1-methyl-4-phenylpyridinium (MPP), in particular, display markedly different inhibitory profiles, with IC50 values for inhibition of MPP transport often being>5-fold greater than ...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Sandoval PJ, Morales MN, Secomb TW, Wright SH Tags: Am J Physiol Renal Physiol Source Type: research

6-Shogaol protects against ischemic acute kidney injury by modulating NF κB and heme oxygenase-1 pathways.
6-Shogaol protects against ischemic acute kidney injury by modulating NFκB and heme oxygenase-1 pathways. Am J Physiol Renal Physiol. 2019 Jul 17;: Authors: Han SJ, Kim M, D'Agati VD, Lee HT Abstract Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy. Ginger is one of the most widely consumed spices in the world and 6-Shogaol, a major Ginger metabolite, has anti-inflammatory effects in neuronal and epithelial cells. Here, we demonstrate that 6-Shogaol treatment protected against renal IR injury with decreased plasma creatinine, ...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Han SJ, Kim M, D'Agati VD, Lee HT Tags: Am J Physiol Renal Physiol Source Type: research

Analysis of Continence Reflexes by Dynamic Urethral Pressure Recordings in a Rat Sress Urinary Incontinence Model induced by Multiple Simulated Birth Traumas.
This study evaluated the real-time changes in urethral pressure during the storage phase using a rat model with stress urinary incontinence (SUI) induced by simulated multiple birth traumas, and investigated the relationship between urethral continence function and dynamic parameters associated with the changes in urethral pressure. Sprague-Dawley rats were divided into sham and 3-times vaginal distention (VD) groups. After transection of T8-9 spinal cord, simultaneous bladder and urethral pressure recordings were performed during intravesical pressure elevation. Then, urodynamic parameters such as leak point pressure (LPP...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Kwon J, Suzuki T, Takaoka E, Shimizu N, Shimizu T, Takai S, Yoshikawa S, de Groat WC, Yoshimura N Tags: Am J Physiol Renal Physiol Source Type: research

Solute and Water Transport along an Inner-medullary Collecting Duct Undergoing Peristaltic Contractions.
In this study, we investigate the mechanism by which about half of the bolus volume is reabsorbed into the collecting duct cells despite the short contact time. To accomplish that, we develop a dynamic mathematical model of solute and water transport along a collecting duct of a rat papilla undergoing peristaltic contractions. The model predicts that, given pre-existing axial concentration gradients along the loops of Henle, approximately 40% of the bolus volume is reabsorbed as the bolus flows down the inner-medullary collecting duct. Additionally, simulation results suggest that while the contraction-induced luminal hydr...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Layton AT Tags: Am J Physiol Renal Physiol Source Type: research

Phosphoproteomic Identification of Vasopressin V2 Receptor-Dependent Signaling in the Renal Collecting Duct.
Abstract Vasopressin controls water balance largely through protein kinase A (PKA)-dependent effects to regulate the collecting-duct water channel aquaporin-2 (AQP2). Although considerable information has accrued regarding regulation of water and solute transport in collecting duct cells, information is sparse regarding the signaling connections between PKA and transport responses. Here, we exploit recent advancements in protein mass spectrometry to carry out a comprehensive, multiple-replicate analysis of changes in the phosphoproteome of native rat inner medullary collecting duct cells in response to the V2-sele...
Source: American Journal of Physiology. Renal Physiology - July 17, 2019 Category: Physiology Authors: Deshpande V, Kao AR, Raghuram V, Datta A, Chou CL, Knepper MA Tags: Am J Physiol Renal Physiol Source Type: research

A mouse model of renal ischemia reperfusion injury solely induced by cold ischemia.
Abstract Transplanted kidneys usually experience several episodes of ischemia, including cold ischemia during allograft storage in preservation solution. However, previous studies focusing on cold renal ischemia was only carried out in vitro or ex vivo. In the present study, we developed and characterized an in vivo mouse model of renal ischemia reperfusion injury (IRI) induced exclusively by cold ischemia. C57BL/6 mice were performed right kidney nephrectomy and left kidney was kept cool with circulating cold saline in a kidney cup, while body temperature was maintained at 37°C. We clamped renal pedicle and f...
Source: American Journal of Physiology. Renal Physiology - July 10, 2019 Category: Physiology Authors: Wei J, Wang Y, Zhang J, Wang L, Fu L, Cha BJ, Buggs J, Liu R Tags: Am J Physiol Renal Physiol Source Type: research

Diagnostic Roles of Urinary Kidney Injury Molecule 1 and Soluble C5b-9 in Acute Tubulointerstitial Nephritis.
Abstract Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury characterized by inflammatory cells infiltrating in the interstitium. The current study aimed to explore non-invasive biomarkers that might indicate activity of pathological injuries and help direct treatment. Fifty-four patients with clinical-pathologically diagnosed ATIN from January 1, 2014 to June 30, 2016 at Peking University First Hospital were enrolled. Urine samples were collected on the morning of renal biopsy and detected for kidney injury molecule-1 (u-KIM-1) and soluble C5b-9 (u-sC5b-9). Immunofluorescence stain...
Source: American Journal of Physiology. Renal Physiology - July 10, 2019 Category: Physiology Authors: Zhao WT, Huang JW, Sun PP, Su T, Tang JW, Wang SX, Liu G, Yang L Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2019 Jul 01;317(1):F218-F219 Authors: PMID: 31282741 [PubMed - in process] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - July 1, 2019 Category: Physiology Tags: Am J Physiol Renal Physiol Source Type: research

P- role of glucocorticoid receptor in glomerular disease.
Abstract Glucocorticoids are potent anti-inflammatory agents that are commonly used in the treatment of various glomerular diseases. Data from in vitro and in vivo studies, in both animals and humans, convincingly demonstrate that glucocorticoids have many beneficial direct effects on glomeruli, including podocytes, suggesting that, in theory, systemic administration is not necessary to achieve therapeutic benefit. Indeed, it is increasingly recognized that systemic steroids often have an unfavorable risk-benefit ratio. As we move into an age of personalized medicine, strategies to develop targeted steroid deliver...
Source: American Journal of Physiology. Renal Physiology - June 5, 2019 Category: Physiology Authors: Goodwin JE Tags: Am J Physiol Renal Physiol Source Type: research

Expression and Distribution of PIEZO1 in the Mouse Urinary Tract.
Abstract The proper function of the organs that make up the urinary tract (kidneys, ureters, bladder, and urethra) depends on their ability to sense and respond to mechanical forces including shear stress and wall tension. Yet, we have limited understanding of the mechanosensors that function in these organs and the tissue sites in which these molecules are expressed. Possible candidates include the stretch-activated PIEZO channels (PIEZO1 and PIEZO2), which are implicated in mechanically regulated body functions including touch sensation, proprioception, lung inflation, and blood pressure regulation. Using report...
Source: American Journal of Physiology. Renal Physiology - June 5, 2019 Category: Physiology Authors: Dalghi MG, Clayton DR, Ruiz WG, Al-Bataineh MM, Satlin LM, Kleyman TR, Ricke WA, Carattino MD, Apodaca G Tags: Am J Physiol Renal Physiol Source Type: research

Effect of Spironolactone for One Year on Endothelial Function and Vascular Inflammation Biomarkers in Renal Transplant Recipients.
BL Abstract BACKGROUND: Kidney transplantation is associated with increased cardiovascular risk. Endothelial dysfunction and vascular inflammation contribute to negative outcome. In experimental models, mineralocorticoid receptor antagonists (MRA) improved endothelial function and reduced inflammation. The current study tested the hypothesis that the MRA spironolactone improves endothelial function and reduces vascular inflammation in renal transplant patients. METHODS: 80 renal transplant patients from an ongoing, double-blind randomized placebo-controlled trial were included. Paired plasma samples before a...
Source: American Journal of Physiology. Renal Physiology - June 5, 2019 Category: Physiology Authors: Mortensen LA, Bistrup C, Stubbe J, Carlström M, Checa A, Wheelock CE, Palarasah Y, Bladbjerg EM, Thiesson HC, Jensen BL Tags: Am J Physiol Renal Physiol Source Type: research

Effect of Renal Tubule-Specific Knockdown of the Na+/H+ Exchanger NHE3 in Akita Diabetic Mice.
Abstract NHE3 contributes to Na+/bicarbonate reabsorption and ammonium secretion in early proximal tubules. To determine its role in the diabetic kidney, type 1 diabetic Akita mice with tubular NHE3 knock-down (Pax8-Cre; NHE3-KO) were generated. NHE3-KO had higher urine pH, more bicarbonaturia, and compensating increases in renal mRNA expression for genes associated with generation of ammonium, bicarbonate and glucose (phosphoenolpyruvate carboxykinase-PEPCK) in proximal tubules and proton and ammonia secretion and glycolysis in distal tubules. This left blood pH and bicarbonate unaffected in non-diabetic and diab...
Source: American Journal of Physiology. Renal Physiology - June 5, 2019 Category: Physiology Authors: Onishi A, Fu Y, Darshi M, Crespo-Masip M, Huang W, Song P, Patel R, Kim YC, Nespoux J, Freeman B, Soleimani M, Thomson SC, Sharma K, Vallon V Tags: Am J Physiol Renal Physiol Source Type: research

Claudin-19 mediates the effects of NO on the paracellular pathway in thick ascending limbs.
Abstract Claudins are a family of tight junction proteins that provide size and charge selectivity to solutes traversing the paracellular space. Thick ascending limbs (THALs) express numerous claudins including claudin-19. NO via cGMP reduces dilution potentials in perfused THALs, a measure of paracellular permeability, but the role of claudin-19 is unknown. We hypothesize that claudin-19 mediates the effects of NO/cGMP on the paracellular pathway in THALs via increases in plasma membrane expression of this protein. We measured the effect of an NO donor spermine NONOate (SPM) on dilution potentials with and withou...
Source: American Journal of Physiology. Renal Physiology - June 5, 2019 Category: Physiology Authors: Monzon CM, Garvin JL Tags: Am J Physiol Renal Physiol Source Type: research

Involvement of PDZ-SAP97 Interactions in Regulating AQP2 Translocation in Response to Vasopressin in LLC-PK1 cells.
Abstract Arginine-vasopressin- (AVP) mediated translocation of aquaporin-2 (AQP2) protein forming water channels from storage vesicles to the membrane of renal collecting ducts is critical for renal conservation of water. The type-1 PDZ-binding motif (PBM) in AQP2 "GTKA" is a critical barcode for its translocation, but its precise role and that of its interacting protein partners in this process remains obscure. We determined that SAP97, a MAGUK protein involved in establishing epithelial cell polarity was an avid binding partner to the PBM of AQP2. The role of the PBM and SAP97 on AQP2 redistribution in...
Source: American Journal of Physiology. Renal Physiology - May 29, 2019 Category: Physiology Authors: Nooh MM, Kale A, Bahouth SW Tags: Am J Physiol Renal Physiol Source Type: research