Sex-Differences in Solute Transport Along the Nephrons: Effects of Na+ Transport Inhibition.
Abstract Each day approximately 1.7kg of NaCl and 180L of water are reabsorbed by nephron segments in humans, with urinary excretion fine-tuned to meet homeostatic requirements. These tasks are coordinated by a spectrum of renal Na+ transporters. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and how those effects may vary between males and females. To accomplish that goal, we developed sex-specific multinephron models that represent detailed transcellular and paracellular transport processes along the...
Source: American Journal of Physiology. Renal Physiology - August 3, 2020 Category: Physiology Authors: Hu R, McDonough AA, Layton AT Tags: Am J Physiol Renal Physiol Source Type: research

Inflammatory mediators in the adipo-renal axis: leptin, adiponectin, and sICAM-1.
CONCLUSION: Both mediation analyses identified an inflammatory (leptin) and an anti-inflammatory (adiponectin) cytokine along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity. PMID: 32744085 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 3, 2020 Category: Physiology Authors: Hua Y, Herder C, Kalhoff H, Buyken AE, Esche J, Krupp D, Wudy SA, Remer T Tags: Am J Physiol Renal Physiol Source Type: research

Ventilatory and chronotropic incompetence during incremental and constant load exercise in end-stage renal disease: a comparative physiology study.
Abstract BACKGROUND: Aerobic capacity is impaired in end-stage renal disease (ESRD), reducing quality of life and longevity. Whilst determinants of maximal exercise intolerance are well defined, little is known of limitation during submaximal exercise. By comparing ESRD and healthy controls, the aim of this study was to characterise mechanisms of exercise intolerance in ESRD by assessing cardiopulmonary physiology at rest and during exercise. METHODS: Resting spirometry and echocardiography were performed in 20 ESRD participants and 20 healthy age and gender matched controls. Exercise tolerance was assessed w...
Source: American Journal of Physiology. Renal Physiology - August 3, 2020 Category: Physiology Authors: McGuire S, Horton EJ, Renshaw D, Chan K, Krishnan N, McGregor G Tags: Am J Physiol Renal Physiol Source Type: research

PF-06869206 is selective inhibitor of renal Pi transport: Evidence from in vitro and in vivo studies.
Abstract Plasma phosphate (Pi) levels are tightly controlled, and elevated plasma Pi levels are associated with an increased risk of cardiovascular complications and death. Two renal transport proteins mediate the majority of Pi reabsorption, the Na+-phosphate cotransporters Npt2a and Npt2c, with Npt2a accounting for 70-80% of Pi reabsorption. The aim of this study was to determine the in vitro effects of a novel Npt2a inhibitor (Npt2a-I, PF-06869206) in opossum kidney (OK) cells as well as determine its selectivity in vivo in Npt2a knockout (Npt2a-/-) mice. In OK cells, Npt2a-I caused dose-dependent reductions of...
Source: American Journal of Physiology. Renal Physiology - August 3, 2020 Category: Physiology Authors: Thomas L, Xue J, Tomilin VN, Pochynyuk OM, Dominguez Rieg JA, Rieg T Tags: Am J Physiol Renal Physiol Source Type: research

Despite initial recovery of GFR long-term renal functions deteriorate following short periods of unilateral ureteral obstruction.
In conclusion, several aspects of renal functions continue to deteriorate following reversal of relatively short periods of UUO despite the initial recovery in GFR. This might stimulate further research in this area and might have clinical implications in terms of determining the best time for intervention following acute ureteral obstruction and long-term monitoring of these individuals. PMID: 32744088 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 3, 2020 Category: Physiology Authors: Hammad FT, Al-Salam S, Hammad WF, Yasin J, Lubbad L Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2020 Aug 01;319(2):F256 Authors: PMID: 32686976 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - July 21, 2020 Category: Physiology Tags: Am J Physiol Renal Physiol Source Type: research

Ultrasound measurement of change in kidney volume is a sensitive indicator of severity of renal parenchymal injury.
Abstract Non-invasive determination of the severity of parenchymal injury in acute kidney injury (AKI) remains challenging. Edema is an early pathological process following injury, which may correlate with changes in kidney volume. The goal of this study was to test the hypothesis that 'increases in kidney volume, measured in vivo using ultrasound correlate with the degree of renal parenchymal injury'. Ischemia reperfusion (IR) of varying length was utilized to produce graded tissue injury. We first determined 1) whether regional kidney volume in rats varied with the severity (0, 15, 30, 45 minutes) of warm bilate...
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Crislip GR, Patel B, Mohamed R, Ray SC, Wei Q, Sun J, Polichnowski A, Sullivan JC, O'Connor PM Tags: Am J Physiol Renal Physiol Source Type: research

T95 Nucleophosmin Phosphorylation as a Novel Mediator and Marker of Regulated Cell Death in Acute Kidney Injury.
Abstract The function of site-specific phosphorylation of nucleophosmin (NPM), an essential Bax chaperone, in stress-induced cell death is unknown. We hypothesized that NPM threonine 95 (T95) phosphorylation both signals and promotes cell death. In resting cells, NPM exclusively resides in the nucleus and threonine 95 is non-phosphorylated. In contrast, phosphorylated T95 NPM (pNPM T95) accumulates in the cytosol after metabolic stress, in multiple human cancer cell lines following gamma radiation, and in post-ischemic human kidney tissue. Based on the T95 phosphorylation consensus sequence, we hypothesized that g...
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Wang Z, Belghasem M, Salih E, Henderson J, Igwebuike C, Havasi A, Borkan SC Tags: Am J Physiol Renal Physiol Source Type: research

Non-esterified free fatty acids (NEFA) enhance the inflammatory response in renal tubules by inducing extracellular ATP release.
Abstract In proteinuric renal diseases, excessive plasma non-esterified free fatty acids (NEFA) bound to albumin can leak across damaged glomeruli to be reabsorbed by renal proximal tubular cells and cause inflammatory tubular cellsdamage by as yet unknown mechanisms. The present study was designed to investigate these mechanisms induced by palmitic acid (PA, one of NEFA) overload. Our results show that excess PA stimulates ATP release through the pannexin1 (Panx1) channel in human renal tubule epithelial cells (HK-2); increasing extracellular ATP (eATP) concentration approximately three-fold in comparison with co...
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Sun H, Sun Z, Varghese Z, Guo Y, Moohread JF, Unwin RJ, Ruan XZ Tags: Am J Physiol Renal Physiol Source Type: research

ANO1 in urethral SMCs contributes to sex differences in urethral spontaneous tone.
Abstract Stress urinary incontinence (SUI) is more common in women than in men, and gender differences in anatomical structure and physiology have been suggested; however, the cellular and molecular mechanisms involved remain unclear. Spontaneous tone of urethra was proved to take the fundamental effect in preventing occurrence of SUI. We investigated whether the urethral spontaneous tone exhibited gender differences. Here, we isolated the urethral smooth muscle and detected the spontaneous tones in female mouse and women. No spontaneous tone was found in male mouse and men. Furthermore, caffeine excited more cont...
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Chen D, Meng W, Shu L, Liu S, Gu Y, Wang X, Feng M Tags: Am J Physiol Renal Physiol Source Type: research

Therapeutic potential of muscle growth promoters in a stress urinary incontinence model.
In conclusion, bimagrumab was the most effective for increasing urethral pressure and continence by promoting injured EUS and pelvic floor muscle recovery. PMID: 32686522 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Yang J, Balog BM, Deng K, Hanzlicek B, Rietsch A, Kuang M, Hatakeyama S, Lach-Trifilieff E, Zhu H, Damaser MS Tags: Am J Physiol Renal Physiol Source Type: research

IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats.
In conclusion, despite male SHR having less IL-10 and IL-10 receptor expression in the kidney compared to females, exogenous IL-10 selectively decreased BP only in males. Furthermore, our data suggests that exogenous IL-10-induced decreases in BP in male SHR are not dependent on upregulating renal NOS activity. PMID: 32686523 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Gillis EE, Musall JB, Baban B, Sullivan JC Tags: Am J Physiol Renal Physiol Source Type: research

Phosphorylation of key podocyte proteins and the association with proteinuric kidney disease.
Abstract Podocyte dysfunction contributes to proteinuric chronic kidney disease. A number of key proteins are essential for podocyte function, including nephrin, podocin, CD2-associated protein (CD2AP), synaptopodin, and a-actinin-4 (ACTN4). Although most of these proteins were first identified through genetic studies associated with human kidney disease, subsequent studies have identified phosphorylation of these proteins as an important post-translational event that regulates their function. In this review, a brief overview of the function of these key podocyte proteins is provided. Second, the role of phosphory...
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Feng D Tags: Am J Physiol Renal Physiol Source Type: research

Mitochondrial Transplantation by Intra-Arterial Injection for Acute Kidney Injury.
In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury (IRI) was investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon-catheters. Following 60 minutes ischemia, the balloon catheters were deflated and the animals received either autologous mitochondria suspended in vehicle or vehicle alone, delivered as a single bolus to the renal arteries. The injected mitochondria were rapidly taken up by the kidney and were distr...
Source: American Journal of Physiology. Renal Physiology - July 20, 2020 Category: Physiology Authors: Doulamis IP, Guariento A, Duignan T, Kido T, Orfany A, Saeed MY, Weixler VH, Blitzer D, Shin B, Snay ER, Inkster JAH, Packard AB, Zurakowski D, Rousselle T, Bajwa A, Parikh SM, Stillman IE, Del Nido PJ, McCully JD Tags: Am J Physiol Renal Physiol Source Type: research

Role of SIRT1 in HIV-associated kidney disease.
Abstract HIV infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We previously showed that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3 were increased in HIVAN kidneys. Here, we demonstrate the key role of SIRT1 deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in...
Source: American Journal of Physiology. Renal Physiology - July 13, 2020 Category: Physiology Authors: Wang X, Liu R, Zhang W, Hyink DP, Das GC, Das B, Li Z, Wang A, Yuan W, Klotman PE, Lee K, He JC Tags: Am J Physiol Renal Physiol Source Type: research

A novel distal convoluted tubule-specific Cre-recombinase driven by the NaCl cotransporter gene.
Abstract Cre-lox technology has revolutionized research in renal physiology by allowing site-specific genetic recombination in individual nephron segments. The distal convoluted tubule (DCT), consisting of distinct early (DCT1) and late (DCT2) segments, plays a central role in Na+ and K+ homeostasis. The only established Cre line targeting the DCT is Pvalb-Cre, which is limited by non-inducibility, activity along DCT1 only, and activity in neurons. Here, we report the characterization of the first Cre line specific to the entire DCT. CRISPR/Cas9 targeting was used to introduce a tamoxifen-inducible IRES-Cre-ERT2 c...
Source: American Journal of Physiology. Renal Physiology - July 13, 2020 Category: Physiology Authors: Cornelius RJ, Sharma A, Su XT, Guo JJ, McMahon JA, Ellison DH, McMahon AP, McCormick JA Tags: Am J Physiol Renal Physiol Source Type: research

Acetazolamide Causes Renal HCO3 ‾ Wasting but Inhibits Ammoniagenesis and Prevents the Correction of Metabolic Acidosis by the Kidney.
Acetazolamide Causes Renal HCO3‾ Wasting but Inhibits Ammoniagenesis and Prevents the Correction of Metabolic Acidosis by the Kidney. Am J Physiol Renal Physiol. 2020 Jul 13;: Authors: Alam P, Amlal S, Thakar CV, Amlal H Abstract Carbonic anhydrase (CAII) binds to the basolateral Na+: HCO3‾ cotransporter (NBCe1) and facilitates HCO3‾ reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats t...
Source: American Journal of Physiology. Renal Physiology - July 13, 2020 Category: Physiology Authors: Alam P, Amlal S, Thakar CV, Amlal H Tags: Am J Physiol Renal Physiol Source Type: research

Hypertensive Female Sprague Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal T regulatory cells.
This study provides insight into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs. PMID: 32597687 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - June 29, 2020 Category: Physiology Authors: Ramirez LA, Gillis EE, Musall JB, Mohamed R, Snyder E, El-Marakby AA, Sullivan JC Tags: Am J Physiol Renal Physiol Source Type: research

Novel Catheter Design Enables Transurethral Catheterization of Male Mice.
Abstract The male mouse is underrepresented in research of the urinary tract due to the difficulty of transurethral catheterization. As a result, there is a lack of analysis of gender differences in urinary tract research. Here, we present a novel catheter design and technique that enables urethral catheterization of male mice. Our catheterization technique uses the resistance met at the level of the external urinary sphincter and prostate to guide the retraction, positioning, and advancement of the catheter into the urinary bladder. We have shown that this method can be used to reproducibly catheterize 12 male mi...
Source: American Journal of Physiology. Renal Physiology - May 28, 2020 Category: Physiology Authors: Lamanna OK, Hsieh MH, Forster CS Tags: Am J Physiol Renal Physiol Source Type: research

14-3-3 gamma, a novel regulator of the large-conductance Ca2+-activated K+ channels.
Abstract 14-3-3 gamma (γ) is a small protein regulating the target proteins through binding to the phosphorylated serine/threonine residues. Sequence analysis of large-conductance Ca2+-activated K+ (BK) channel revealed a putative 14-3-3 binding site in the C-terminal region. Our previous data showed that 14-3-3γ is widely expressed in the mouse kidney. We, therefore, hypothesized that 14-3-3γ has a novel role in the regulation of BK channel activity and protein expression. We first demonstrated the interaction of 14-3-3γ with BKα by co-immunoprecipitation. In HEK293 cells stably expr...
Source: American Journal of Physiology. Renal Physiology - May 28, 2020 Category: Physiology Authors: Chen S, Feng X, Chen X, Zhuang Z, Xiao J, Fu H, Klein JD, Wang XH, Hoover RS, Eaton DC, Cai H Tags: Am J Physiol Renal Physiol Source Type: research

The differential effects of low dose sacubitril and/or valsartan on renal disease in salt-sensitive hypertension.
Abstract Diuretics and renin-angiotensin system (RAAS) blockers are often insufficient to control the blood pressure (BP) in salt-sensitive (SS) subjects. Abundant data support the proposal that level of Atrial Natriuretic Peptide (ANP) may correlate with pathogenesis of SS hypertension. We hypothesized here that increasing ANP level with sacubitril, combined with RAAS blockage by valsartan, can be beneficial for alleviation of renal damage in a model of SS hypertension, the Dahl SS rat. To induce a BP increase, the rats were challenged with a high salt 4% NaCl diet for 21 days, and chronic administration of vehic...
Source: American Journal of Physiology. Renal Physiology - May 28, 2020 Category: Physiology Authors: Polina I, Domondon M, Fox R, Sudarikova A, Troncoso M, Vasileva V, Kashyrina Y, Beck Gooz M, Schibalski R, DeLeon-Pennell KY, Fitzgibbon WR, Ilatovskaya DV Tags: Am J Physiol Renal Physiol Source Type: research

NF- κB blockade during short-term L-NAME and salt overload strongly attenuates the late development of chronic kidney disease.
NF-κB blockade during short-term L-NAME and salt overload strongly attenuates the late development of chronic kidney disease. Am J Physiol Renal Physiol. 2020 May 28;: Authors: Carneiro Oliveira K, Fregnan Zambom FF, Albino AH, Costa Alarcon Arias S, Ferreira Ávila V, Dias Faustino V, Avancini Costa Malheiros DM, Olsen Saraiva Camara N, Kazue Fujihara C, Zatz R Abstract NO synthase inhibition by L-NAME plus high-salt diet (HS) is a model of Chronic Kidney Disease (CKD) characterized by marked hypertension and renal injury. With cessation of treatment, most of these changes subside, but pr...
Source: American Journal of Physiology. Renal Physiology - May 28, 2020 Category: Physiology Authors: Carneiro Oliveira K, Fregnan Zambom FF, Albino AH, Costa Alarcon Arias S, Ferreira Ávila V, Dias Faustino V, Avancini Costa Malheiros DM, Olsen Saraiva Camara N, Kazue Fujihara C, Zatz R Tags: Am J Physiol Renal Physiol Source Type: research

Renal ischemia alters expression of mitochondria-related genes and impairs mitochondrial structure and function in swine scattered tubular-like cells.
Abstract Scattered tubular-like cells (STCs) are dedifferentiated surviving tubular epithelial cells that repair neighboring injured cells. Experimental renal artery stenosis (RAS) impairs STC reparative potency by inducing mitochondrial injury, but the exact mechanisms of mitochondrial damage remains unknown. We hypothesized that RAS alters expression of mitochondria-related genes, contributing to mitochondrial structural damage and dysfunction in swine STCs. CD24+/CD133+ STCs were isolated from pig kidneys after 10 weeks of RAS or sham (n=3 each). mRNA sequencing was performed and nuclear-DNA (nDNA) encoded mito...
Source: American Journal of Physiology. Renal Physiology - May 28, 2020 Category: Physiology Authors: Farahani RA, Zhu XY, Tang H, Jordan KL, Lerman LO, Eirin A Tags: Am J Physiol Renal Physiol Source Type: research

Normal range urine albumin excretion associates with blood pressure and renal electrolyte handling in pregnancy.
CONCLUSIONS: At gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders. PMID: 32463729 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - May 28, 2020 Category: Physiology Authors: Birukov A, Andersen MS, Jørgensen JS, Kitlen G, Rakova N, Nielsen JH, Andersen LB, Dechend R, Jensen BL Tags: Am J Physiol Renal Physiol Source Type: research

Monophosphoryl lipid A pretreatment suppresses sepsis- and LPS-induced proinflammatory cytokine production in medullary thick ascending limb.
In this study, we show that TNF-α expression is increased in medullary thick ascending limbs (MTAL) of mice with sepsis induced by cecal ligation and puncture. Treatment with LPS for 3 h in vitro also increased MTAL TNF-α production. Sepsis and LPS increased MTAL TNF-α expression through activation of an MyD88-IRAK-1-ERK signaling pathway. Pretreatment with monophosphoryl lipid A (MPLA), a nontoxic immunomodulator that protects against bacterial infection, eliminated the sepsis- and LPS-induced increases in MTAL TNF-α production. The suppressive effect of MPLA on TNF-α was mediated through act...
Source: American Journal of Physiology. Renal Physiology - May 18, 2020 Category: Physiology Authors: Watts BA, Tamayo EH, Sherwood ER, Good DW Tags: Am J Physiol Renal Physiol Source Type: research

Sex differences in endothelial function in chronic kidney disease.
SEX DIFFERENCES IN ENDOTHELIAL FUNCTION IN CHRONIC KIDNEY DISEASE. Am J Physiol Renal Physiol. 2020 May 18;: Authors: Kruse NT, You Z, Moreau KL, Kendrick J, Jalal D Abstract Vascular dysfunction plays an important role in the etiology of chronic kidney disease (CKD), and is associated with cardiovascular diseases (CVD). Sex differences in vascular function are common in clinical and non-clinical populations. However, no data exist in individuals with CKD. The following study tested the hypothesis that sex and/or aging differences exist on vascular function in patients with CKD. Endothelium dependent ...
Source: American Journal of Physiology. Renal Physiology - May 18, 2020 Category: Physiology Authors: Kruse NT, You Z, Moreau KL, Kendrick J, Jalal D Tags: Am J Physiol Renal Physiol Source Type: research

Is the kidney a target of SARS-CoV-2?
la NA Abstract The new disease produced by the Severe Acute Respiratory Syndrome - coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multi-organ failure. Like other coronaviruses, SARS-CoV-2 recognizes the human Angiotensin Converting Enzyme 2 (hACE2) as a cellular receptor that allows it to infect different host cells, and likely disrupts the renin...
Source: American Journal of Physiology. Renal Physiology - May 15, 2020 Category: Physiology Authors: Martínez-Rojas MA, Vega-Vega O, Bobadilla NA Tags: Am J Physiol Renal Physiol Source Type: research

Open microfluidic coculture reveals paracrine signaling from human kidney epithelial cells promotes kidney specificity of endothelial cells.
Abstract Endothelial cells (ECs) from different human organs possess organ-specific characteristics that support specific tissue regeneration and organ development. EC specificity are identified by both intrinsic and extrinsic cues, among which, parenchyma and organ-specific microenvironment are critical contributors. These extrinsic cues are, however, largely lost during ex vivo cultures. Outstanding challenges remain to understand and re-establish EC organ-specificity for in vitro studies to recapitulate human organ-specific physiology. Here, we designed an open microfluidic platform to study the role of human k...
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Zhang T, Lih D, Nagao RJ, Xue J, Berthier E, Himmelfarb J, Zheng Y, Theberge AB Tags: Am J Physiol Renal Physiol Source Type: research

Dietary fructose enhances angiotensin II-stimulated Na transport via activation of PKC α in renal proximal tubules.
Dietary fructose enhances angiotensin II-stimulated Na transport via activation of PKCα in renal proximal tubules. Am J Physiol Renal Physiol. 2020 May 11;: Authors: Yang N, Hong NJ, Garvin JL Abstract Angiotensin II (Ang II) stimulates proximal nephron transport via activation of classical protein kinase C (PKC) isoforms. Acute fructose treatment stimulates PKC and dietary fructose enhances Ang II's ability to stimulate Na transport, but the mechanisms are unclear. We hypothesized that dietary fructose enhances Ang II's ability to stimulate renal proximal tubule Na reabsorption by augmenting PK...
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Yang N, Hong NJ, Garvin JL Tags: Am J Physiol Renal Physiol Source Type: research

GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in pre-hypertensive rats.
Sorensen CM Abstract Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate postprandial insulin release. However, GLP-1 also exerts extra-pancreatic effects including renal effects. Some of these renal effects are attenuated in hypertensive rats, where renal expression of GLP-1 receptors is reduced. Here, we assessed expression and vascular function of GLP-1 receptors in kidneys from young pre-hypertensive rats. We also examined GLP-1-induced vasodilation in the renal vasculature in wild-type (WT) and GLP-1 receptor knock-out (KO) mice using wire- and pressure-myography and the isolated perfuse...
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Jensen EP, Møller S, Hviid AVR, Veedfald S, Holst JJ, Pedersen J, Ørskov C, Sorensen CM Tags: Am J Physiol Renal Physiol Source Type: research

Developmental loss, but not pharmacological suppression, of renal carbonic anhydrase 2 results in pyelonephritis susceptibility.
We examined the effect of pharmacological CA suppression using acetazolamide in an experimental murine UTI model. Car2-/- vs wild type mice were compared for differences in renal innate immunity. In our transplant scheme, mice only lacking CA-II in the kidney had increased pyelonephritis risk. Mice treated with acetazolamide had lower kidney bacterial burdens at 6-hours post-infection which appeared to be due to tubular flow from diuresis because comparable results were obtained when furosemide was substituted for acetazolamide. Isolated Car2-/-kidney cells enriched for intercalated cells demonstrate altered intercalated c...
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Ketz J, Saxena V, Arregui S, Jackson AR, Schwartz GJ, Yagisawa T, Fairchild RL, Hains DS, Schwaderer AL Tags: Am J Physiol Renal Physiol Source Type: research

Depletion of macrophages slows the early progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant rats.
Abstract Recently, we reported that obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats display progressive renal injury. The current study demonstrated that the early development of renal injury in the SSLepRmutant strain is associated with an increase in the renal infiltration of macrophages compared to lean SS rats. We also examined whether depletion of macrophages with clodronate would reduce the early progression of renal injury in the SSLepRmutant strain. Four week-old SS and SSLepRmutant rats were treated with either vehicle (PBS) or clodronate (50 mg/kg, i.p., twice/week) for 4 weeks. Whil...
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Poudel B, Shields CA, Brown AK, Ekperikpe US, Johnson TD, Cornelius DC, Williams JM Tags: Am J Physiol Renal Physiol Source Type: research

CBX7 suppression prevents kidney against ischemia and reperfusion injury induced endoplasmic reticulum stress through Nrf-2/HO-1 pathway.
In conclusion, our results demonstrated that CBX7 inhibition alleviated AKI by preventing endoplasmic reticulum stress via Nrf2/HO-1 pathway, indicating that CBX7 inhibitor could be a potential therapeutic target for renal I/R injury. PMID: 32390514 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Zhang Y, Zhang JJ, Liu XH, Wang L Tags: Am J Physiol Renal Physiol Source Type: research

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and its pathway involved.
This study investigated if IL6 influenced ECM protein production by MCs and the regulatory pathways involved. Experiments were carried out in cultured human MCs (HMCs) and in mice. We found that overexpressing IL6 and its receptor decreased the abundance of fibronectin and collagen IV in MCs. Enzyme-linked immunosorbent assay and immunoblot analysis demonstrated that thapsigargin (an activator of store-operated Ca2+ entry, SOCE), but not endoplasmic reticular stress inducer tunicamycin, significantly increased IL6 content. This thapsigargin effect was abolished by GSK-7975A, a selective inhibitor of SOCE, and by silencing ...
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Chaudhari S, Yazdizadeh Shotorbani P, Tao Y, Davis ME, Mallet RT, Ma R Tags: Am J Physiol Renal Physiol Source Type: research

Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of glomerular filtration barrier.
Abstract Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies revealed that Tns2-deficient mice exhibited defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by Tns2 deficiency remain unidentified. Here, we aimed to determine the role of Tns2 using newborn Tns2-deficient mice and murine primary podocytes. Ultrastructural analysis revealed that the developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin &alph...
Source: American Journal of Physiology. Renal Physiology - May 11, 2020 Category: Physiology Authors: Uchio-Yamada K, Yasuda K, Monobe Y, Akagi KI, Suzuki O, Manabe N Tags: Am J Physiol Renal Physiol Source Type: research

Sensitivity of urethral flow-evoked voiding reflexes decline with age in rat: insights into age-related underactive bladder.
Abstract The prevalence of underactive bladder (UAB) increases with age, suggesting a link between age-related processes and lower urinary tract (LUT) symptoms; however, the underlying mechanisms of age-related UAB are poorly understood. Understanding how aging affects LUT reflexes may help development of new treatments by identifying mechanistic targets. In this work, we study the relationship between age and systems-level function of the LUT and test the hypothesis that aging is related to weakening of reflexes that control voiding. Three groups of anesthetized female rats, young (4-7 months), mature (11-14 mont...
Source: American Journal of Physiology. Renal Physiology - May 4, 2020 Category: Physiology Authors: Geramipour A, Danziger Z Tags: Am J Physiol Renal Physiol Source Type: research

Effects of extreme potassium stress on blood pressure and renal tubular sodium transport.
Abstract We characterized mouse blood pressure and ion transport in the setting of commonly used rodent diets that drive potassium intake to the extremes of deficiency and excess. Male 129S2/Sv mice were fed either K+ deficient, control, high K+ basic, or high KCl diets for 10 days. Mice maintained on a K+ deficient diet exhibited no change in blood pressure, whereas K+ loaded mice developed a ~10 mmHg blood pressure increase. Following challenge with NaCl, K+ deficient mice developed a salt-sensitive 8 mmHg increase in blood pressure, whereas blood pressure was unchanged in mice fed high K+ diets. Notably, 10 day...
Source: American Journal of Physiology. Renal Physiology - April 13, 2020 Category: Physiology Authors: Boyd-Shiwarski CR, Weaver CJ, Beacham RT, Shiwarski DJ, Connolly KA, Nkashama LJ, Mutchler S, Griffiths SE, Knoell SA, Sebastiani RS, Ray EC, Marciszyn AL, Subramanya AR Tags: Am J Physiol Renal Physiol Source Type: research

Let's Not Take Voiding for Granted.
PMID: 32281416 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - April 13, 2020 Category: Physiology Authors: Zderic SA Tags: Am J Physiol Renal Physiol Source Type: research

TCR+CD4-CD8- (double negative) T cells protect from cisplatin-induced renal epithelial cell apoptosis and acute kidney injury.
In this study, wild type (WT) mice were treated with cisplatin (30mg/kg) or vehicle and the effect on kidney DN T cell numbers and function were measured. In vitro studies evaluated effects of kidney DN T cells on cisplatin-induced apoptosis and PD ligand 1 (PDL1) in renal epithelial cells. Adoptive transfer studies assessed therapeutic potential of DN T cells during cisplatin-induced AKI. Our results show that kidney DN T cell population increased at 24 hours and declined by 72 hours after cisplatin treatment. Cisplatin treatment increased kidney DN T cell proliferation, apoptosis, CD69 and IL10 expression whereas CD62L, ...
Source: American Journal of Physiology. Renal Physiology - April 13, 2020 Category: Physiology Authors: Gong J, Noel S, Hsu J, Bush EL, Arend LJ, Sadasivam M, Lee SA, Kurzhagen JT, Hamad ARA, Rabb H Tags: Am J Physiol Renal Physiol Source Type: research

Resuscitation with pegylated-carboxyhemoglobin preserves renal cortical oxygenation and improves skeletal muscle microcirculatory flow during endotoxemia.
Abstract PEGylated-carboxyhemoglobin (PEGHbCO), which has carbon monoxide-releasing properties, plasma expansion and oxygen-carrying properties, may improve both skeletal microcirculatory flow and renal cortical microcirculatory partial oxygen pressure (CµPO2) and subsequently limit endotoxemia-induced acute kidney injury (AKI). Anesthetized, ventilated Wistar albino rats (n=44) underwent endotoxemic shock. CµPO2 was measured in exposed kidneys using a phosphorescence-quenching method. Rats were randomly assigned to five groups: (1) unresuscitated lipopolysaccharide (LPS); (2) Ringer's acetate (LPS+RA)...
Source: American Journal of Physiology. Renal Physiology - April 13, 2020 Category: Physiology Authors: Guerci P, Ergin B, Kandil A, Ince Y, Heeman P, Hilty MP, Bakker J, Ince C Tags: Am J Physiol Renal Physiol Source Type: research

Western diet induces renal artery endothelial stiffening that is dependent on the epithelial sodium channel.
Abstract Consumption of a western diet (WD) induces central aortic stiffening that contributes to transmittance of pulsatile blood flow to end organs including the kidney. Our recent work support that endothelial epithelial sodium channel (EnNaC) expression and activation enhances aortic endothelial cell stiffening through reductions in endothelial nitric oxide (NO) synthase (eNOS) and bioavailable NO that result in inflammatory/oxidant responses and perivascular fibrosis. However, the role that EnNaC activation has on endothelial responses in the renal circulation remain unknown. We hypothesized that cell-specifi...
Source: American Journal of Physiology. Renal Physiology - April 13, 2020 Category: Physiology Authors: Xiong Y, Aroor AR, Ramirez-Perez FI, Jia G, Habibi J, Manrique-Acevedo C, Lastra G, Chen D, DeMarco VG, Martinez-Lemus LA, Hill MA, Jaisser F, Sowers JR, Whaley-Connell A Tags: Am J Physiol Renal Physiol Source Type: research

Urine Cytokines as Biomarkers for Diagnosing Interstitial Cystitis/Bladder Pain Syndrome and Mapping Its Clinical Characteristics.
CONCLUSIONS: IC/BPS patients had urine cytokine profiles that clearly differed from those of controls. Urine cytokines might be useful as biomarkers for diagnosing IC/BPS and mapping its clinical characteristics. PMID: 32281420 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - April 13, 2020 Category: Physiology Authors: Jiang YH, Jhang JF, Hsu YH, Ho HC, Wu YH, Kuo HC Tags: Am J Physiol Renal Physiol Source Type: research

Comprehensive assessment of mitochondrial respiratory function in freshly isolated nephron segments.
Abstract Changes in mitochondrial function are central to many forms of kidney disease including acute injury, diabetic nephropathy, hypertension and chronic kidney diseases. As such, there is an increasing need for reliable and fast methods for assessing mitochondrial respiratory function in renal cells. Despite being indispensable for many mechanistic studies, cultured cells or isolated mitochondria, however, often do not recapitulate in vivo or close-to-in vivo situations. Cultured and/or immortalized cells often change their bioenergetic profile and phenotype compared to in vivo or ex vivo situations, and isol...
Source: American Journal of Physiology. Renal Physiology - March 30, 2020 Category: Physiology Authors: McCrimmon A, Domondon M, Sultanova R, Ilatovskaya DV, Stadler K Tags: Am J Physiol Renal Physiol Source Type: research

The effects of uric acid dysregulation on the kidney.
Abstract Recently, research has redirected its interests in uric acid (UA) from gout, an inflammatory disease in joints, to groups of closely interrelated pathologies associated with cardiovascular and kidney dysfunction. Many epidemiological, clinical, and experimental studies have shown that UA may play a role in the pathophysiology of the cardiorenal syndrome continuum; however, it is still unclear if it is a risk factor or a causal role. Hyperuricemia has been well studied in the past two decades, revealing mechanistic insights into UA homeostasis. Likewise, some epidemiological and experimental evidence sugge...
Source: American Journal of Physiology. Renal Physiology - March 30, 2020 Category: Physiology Authors: Dissanayake LV, Spires DR, Palygin O, Staruschenko A Tags: Am J Physiol Renal Physiol Source Type: research

Uric acid and inflammation in kidney disease.
Abstract Asymptomatic hyperuricemia is frequently observed in patients with kidney disease. Although a substantial number of epidemiologic studies have suggested that an elevated uric acid level plays a causative role in the development and progression of kidney disease, whether hyperuricemia is simply a result of decreased renal excretion of uric acid or is a contributor to kidney disease remains a matter of debate. Over the last two decades, multiple experimental studies have expanded the knowledge of the biological effects of uric acid beyond its role in gout. In particular, uric acid induces immune system acti...
Source: American Journal of Physiology. Renal Physiology - March 30, 2020 Category: Physiology Authors: Jung SW, Kim SM, Kim YG, Lee SH, Moon JY Tags: Am J Physiol Renal Physiol Source Type: research

Hypertension Induces Glomerulosclerosis in Phospholipase C Epsilon 1 Deficiency.
Abstract Loss-of-function mutations in phospholipase C epsilon (PLCE1) have been detected in patients with nephrotic syndrome, but other family members with the same mutation were asymptomatic, suggesting additional stressor are required to cause the full phenotype. Consistent with these observations, we determined that global Plce1-deficient mice have histologically normal glomeruli and no albuminuria at baseline. Angiotensin II (Ang II) is known to induce glomerular damage in genetically susceptible individuals. Therefore, we tested whether Ang II enhances glomerular damage in Plce1-deficient mice. Ang II increa...
Source: American Journal of Physiology. Renal Physiology - March 30, 2020 Category: Physiology Authors: Atchison DK, O'Connor CL, Menon R, Otto EA, Ganesh SK, Wiggins RC, Smrcka AV, Bitzer M Tags: Am J Physiol Renal Physiol Source Type: research

Transplanted senescent renal scattered tubular-like cells induce injury in the mouse kidney.
Abstract Cellular senescence, a permanent arrest of cell proliferation, is characterized by a senescence-associated secretory phenotype (SASP), which reinforces senescence and exerts noxious effects on adjacent cells. Recent studies suggest that transplanting small numbers of senescent cells suffices to provoke tissue inflammation. We hypothesized that senescent cells can directly augment renal injury. Primary scattered tubular-like cells (STC) acquired from pig kidneys were irradiated by 10Gy of cesium radiation, and 3 weeks later cells were characterized for levels of senescence and SASP markers. Control or sene...
Source: American Journal of Physiology. Renal Physiology - March 30, 2020 Category: Physiology Authors: Kim SR, Jiang K, Ferguson CM, Tang H, Chen XJ, Zhu XY, Hickson LJ, Tchkonia T, Kirkland JL, Lerman LO Tags: Am J Physiol Renal Physiol Source Type: research

The potential risk of kidney vulnerable to novel coronavirus 2019 infection.
PMID: 32223555 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - March 30, 2020 Category: Physiology Authors: Zhang F, Liang Y Tags: Am J Physiol Renal Physiol Source Type: research

Increased fibrotic signaling in a murine model for intra-arterial contrast induced acute kidney Injury (CI-AKI).
Abstract Contrast-induced acute kidney injury (CI-AKI) is a vexing problem and more than 70 million patients undergo studies utilizing iodinated contrast. The molecular mechanisms responsible for CI-AKI are poorly understood. The goal of the present paper was to determine the role of tissue growth factor-beta1 (TGF-β1)/ mothers against decapentaplegic homolog 3 (SMAD3) signaling and associated collagen expression in a murine model of intraarterial CI-AKI. Murine model of CI-AKI after intra-arterial contrast agent administration was created by first performing a partial nephrectomy to induce chronic kidney dis...
Source: American Journal of Physiology. Renal Physiology - March 23, 2020 Category: Physiology Authors: Sharma A, Kilari S, Cai C, Simeon ML, Misra S Tags: Am J Physiol Renal Physiol Source Type: research

Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease.
Abstract Protease-activated receptors (PARs) are coagulation protease targets, and they increase expression of inflammatory cytokines and chemokines in various diseases. Of all PARs, previous reports show that PAR1 or PAR2 inhibition is protective against diabetic glomerular injury. However, how PAR1 and PAR2 cooperatively contribute to DKD pathogenesis and whether dual blockade of PARs is more effective in DKD remains elusive. To address this issue, male type I diabetic Akita mice heterozygous for endothelial nitric oxide synthase were used as a model of DKD. Four month-old mice were divided into four treatment g...
Source: American Journal of Physiology. Renal Physiology - March 23, 2020 Category: Physiology Authors: Mitsui S, Oe Y, Sekimoto A, Sato E, Hashizume Y, Yamakage S, Kumakura S, Sato H, Ito S, Takahashi N Tags: Am J Physiol Renal Physiol Source Type: research