TRPV4 blockade reduces voiding frequency, ATP release and pelvic sensitivity in mice with chronic urothelial overexpression of NGF (NGF-OE).
Abstract Transient receptor potential vanilloid family member 4 (TRPV4) transcript and protein expression increased in the urinary bladder and lumbosacral DRG of transgenic mice with chronic, urothelial overexpression of NGF (NGF-OE) mice. We have evaluated the functional role of TRPV4 in bladder function with open outlet cystometry, void spot assays, and natural voiding assays (Urovoid) with a TRPV4 antagonist, HC067047 (1 μM) or vehicle in NGF-OE and littermate WT mice. Blockade of TRPV4 at the level of the urinary bladder significantly (p ≤ 0.01) increased intercontraction interval (ICI, 2.2-fold), void v...
Source: Am J Physiol Renal P... - October 21, 2019 Category: Urology & Nephrology Authors: Girard BM, Campbell SE, Perkins M, Hsiang H, Tooke K, Drescher C, Hennig GW, Heppner TJ, Nelson MT, Vizzard MA Tags: Am J Physiol Renal Physiol Source Type: research

Knockout of P2rx7 purinergic receptor attenuates cyst growth in a rat model of ARPKD.
Abstract The severity of polycystic kidney diseases depends on the counterbalancing of genetic predisposition and environmental factors exerting permissive or protective influence on cyst development. One poorly characterized phenomenon in the cystic epithelium is abnormal purinergic signaling. Earlier experimental studies revealed high importance of the ionotropic P2X receptors (particularly, P2X7) in the pathophysiology of the cyst wall. To study mechanisms of P2X7 involvement in cyst growth and the aspects of targeting these receptors in PKD treatment we performed a CRISPR/SpCas9-mediated global knockout of the...
Source: Am J Physiol Renal P... - October 21, 2019 Category: Urology & Nephrology Authors: Arkhipov SN, Potter DL, Geurts AM, Pavlov TS Tags: Am J Physiol Renal Physiol Source Type: research

Stem cell-derived extracellular vesicles for renal repair: Do cardiovascular comorbidities matter?
Abstract Extracellular vesicle (EV)-based regenerative therapy has shown promising results in preclinical models of renal disease and might be useful for patients with several forms of chronic kidney disease (CKD). However, individuals with CKD often present with comorbidities, including obesity, hypertension, diabetes, or even metabolic syndrome, which may alter the endogenous characteristics and impair the reparative capacity of stem cells and their daughter EVs. This brief review summarizes evidence of alterations in the morphology, cargo, and function of mesenchymal stem cells (MSCs) and MSC-derived EVs in the...
Source: Am J Physiol Renal P... - October 21, 2019 Category: Urology & Nephrology Authors: Eirin A, Lerman LO Tags: Am J Physiol Renal Physiol Source Type: research

The case for capillary rarefaction in the AKI to CKD progression: insights from multiple injury models.
PMID: 31630545 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 21, 2019 Category: Urology & Nephrology Authors: Basile DP Tags: Am J Physiol Renal Physiol Source Type: research

Differential Expression of Parietal Epithelial Cell and Podocyte Extracellular Matrix Proteins in Focal Segmental Glomerulosclerosis and Diabetic Nephropathy.
This study aimed to define individual ECM protein isoform expression by PECs in both experimental and human focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN), and to determine if changes were CD44-dependent. In experimental FSGS induced with a cytotoxic podocyte antibody, and in the BTBR ob/ob mouse model of DN, PEC-derived protein staining was significantly increased in PECs. Dual staining also showed de novo expression of the podocyte-specific ECM proteins LAMB2 and Agrin in PECs. Similar findings were observed in biopsies from patients with FSGS and DN. Increases in individual ECM proteins co-local...
Source: Am J Physiol Renal P... - October 21, 2019 Category: Urology & Nephrology Authors: Chan GC, Eng DG, Miner JH, Alpers CE, Hudkins KL, Chang A, Pippin JW, Shankland SJ Tags: Am J Physiol Renal Physiol Source Type: research

Intrauterine low-protein diet aggravates developmental abnormalities of the urinary system via the Akt/Creb3 pathway in Robo2 mutant mice.
This study aimed to establish an intrauterine low protein diet Robo2 mutant mouse model and found that intrauterine low-protein diet led to significantly increased CAKUT phenotypes in Robo2PB/+ mice offspring, dominant by a duplicated collecting system. At the same time, more ectopic and lower-located ureteric buds (UB) were observed under intrauterine low-protein diet Robo2 mutant mouse model and the number of UB branches was reduced in the serum-free culture. During UB protrusion, intrauterine low-protein diet reduced the expression of Slit2/Robo2 in the Robo2 mutant mice and affected the expression of Gdnf/Ret, which is...
Source: Am J Physiol Renal P... - October 21, 2019 Category: Urology & Nephrology Authors: Yu M, Tan L, Li Y, Chen J, Zhai Y, Rao J, Fang X, Wu X, Xu H, Shen Q Tags: Am J Physiol Renal Physiol Source Type: research

JTZ-951, a HIF prolyl hydroxylase inhibitor, suppresses renal interstitial fibroblast transformation and expression of fibrosis-related factors.
Abstract Some preceding studies have provided evidence that hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PH inhibitors) have therapeutic potential against tubular interstitial fibrosis (TIF). Recently, transformation of renal interstitial fibroblasts (RIFs) into alpha smooth muscle actin (αSMA)- positive myofibroblasts with loss of their hypoxia-inducible EPO expression has been hypothesized as the central mechanism responsible for TIF with renal anemia (the RIF hypothesis). These reports suggest that HIF-PH inhibitors may suppress TIF via suppressing transformation of RIFs. However, the direc...
Source: Am J Physiol Renal P... - October 21, 2019 Category: Urology & Nephrology Authors: Wakashima T, Tanaka T, Fukui K, Komoda Y, Shinozaki Y, Kobayashi H, Matsuo A, Nangaku M Tags: Am J Physiol Renal Physiol Source Type: research

Parenteral Iron Sucrose-Induced Renal Preconditioning: Differential Ferritin Heavy and Light Chain Expression in Plasma, Urine and Internal Organs.
Abstract Experimental data suggest that iron sucrose (FeS) injection, used either alone or in combination with other pro-oxidants, can induce "renal preconditioning", in part, by up-regulating cytoprotective ferritin levels. However, the rapidity, degree, composition (heavy vs. light chain), and renal ferritin changes following FeS administration in humans remain to be defined. To address these issues, healthy human volunteers (HVs; n,9) and stage 3-4 CKD patients (n,9) were injected once with FeS (120, 240, or 360 mg). Plasma ferritin was measured from 0-8 days post-injection as an overall index of ferr...
Source: Am J Physiol Renal P... - October 14, 2019 Category: Urology & Nephrology Authors: Johnson AC, Gooley T, Guillem A, Keyser J, Rasmussen H, Singh B, Zager RA Tags: Am J Physiol Renal Physiol Source Type: research

The soluble guanylate cyclase stimulator praliciguat attenuates inflammation, fibrosis, and end-organ damage in the Dahl model of cardiorenal failure.
Abstract Reduced nitric oxide (NO) and a decrease in cyclic guanosine monophosphate (cGMP) signaling mediated by soluble guanylate cyclase (sGC) has been linked to development of several cardiorenal diseases. Stimulating sGC is a potential means for enhancing cGMP production in conditions of reduced NO bioavailability. The purpose of our studies was to determine the effects of praliciguat, a clinical-stage sGC stimulator, in a model of cardiorenal failure. Dahl salt-sensitive (DSS) rats fed a high-salt diet to induce hypertension and organ damage were treated with the sGC stimulator praliciguat to determine its ef...
Source: Am J Physiol Renal P... - October 14, 2019 Category: Urology & Nephrology Authors: Shea CM, Price GM, Liu G, Sarno R, Buys ES, Currie MG, Masferrer JL Tags: Am J Physiol Renal Physiol Source Type: research

Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea.
Conclusions CPAP use was associated with improved renal hemodynamics in both sexes, and down-regulated renal RAS activity in women but not men. PMID: 31608672 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 14, 2019 Category: Urology & Nephrology Authors: Nicholl DDM, Hanly PJ, Zalucky A, Handley G, Sola DY, Ahmed S Tags: Am J Physiol Renal Physiol Source Type: research

Sympathetic regulation of the NCC in norepinephrine-evoked salt-sensitive hypertension in Sprague-Dawley rats.
Abstract Salt sensitivity of blood pressure is characterized by inappropriate sympathoexcitation and renal sodium reabsorption during high salt intake. In salt-resistant animal models, exogenous norepinephrine infusion promotes salt-sensitive hypertension and prevents dietary sodium-evoked suppression of the sodium chloride cotransporter (NCC). Studies of the adrenergic signaling pathways that modulate NCC activity during norepinephrine infusion have yielded conflicting results implicating α1- and/or β-adrenoceptors and a downstream kinase network that phosphorylates and activates the NCC, including wit...
Source: Am J Physiol Renal P... - October 14, 2019 Category: Urology & Nephrology Authors: Frame AA, Puleo F, Kim K, Walsh KR, Faudoa E, Hoover RS, Wainford RD Tags: Am J Physiol Renal Physiol Source Type: research

Resilience to acute kidney injury in offspring of maternal protein restriction.
ambrano E, Bobadilla NA Abstract Protein restriction (PR) during pregnancy induces morphofunctional alterations related to deficient nephrogenesis. We studied the renal functional and morphological significance of PR during pregnancy and/or lactation in adult male rat offspring and the repercussions on acute kidney injury severity. Female rats were randomly assigned to the following groups: control diet during pregnancy and lactation (C); control diet during pregnancy and PR diet during lactation (CR); PR during pregnancy and control diet during lactation (RC); and PR during pregnancy and lactation (RR). Three mon...
Source: Am J Physiol Renal P... - October 14, 2019 Category: Urology & Nephrology Authors: García-Ortuño LE, Barrera-Chimal J, Pérez-Villalva R, Ortega Trejo JA, Luna-Bolaños E, Lima-Posada IQ, Sanchez-Navarro A, Reyes-Castro LA, Gamba G, Zambrano E, Bobadilla NA Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +67 new citations
67 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2019/09/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - September 18, 2019 Category: Urology & Nephrology Tags: Report Source Type: research

Am J Physiol Renal Physiol; +18 new citations
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2019/09/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - September 11, 2019 Category: Urology & Nephrology Tags: Report Source Type: research

Am J Physiol Renal Physiol; +75 new citations
75 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2019/09/05PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - September 5, 2019 Category: Urology & Nephrology Tags: Report Source Type: research

Complement C3 exacerbates renal interstitial fibrosis by facilitating the M1 macrophage phenotype in a mouse model of unilateral ureteral obstruction.
In this study, we investigated the contribution of C3 on macrophage polarization and renal fibrosis in C3 deficient unilateral ureteral obstruction (UUO) mice and bone marrow-derived macrophages (BMDMs). C3 deficient mice exhibited attenuated renal fibrosis and ameliorated peritubular capillary rarefaction. Lack of C3 contributed to M2 macrophage polarization, increased IL-10 and VEGF164, decreased TNF-α and sVEGFR1 expression in the obstructed kidneys at the early stages of UUO. C3a facilitated LPS-induced M1 polarization and inflammatory factor production in BMDM in vitro, accompanied by increased ERK, NF-κB,...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Cui J, Wu X, Song Y, Chen Y, Wan J Tags: Am J Physiol Renal Physiol Source Type: research

Renal oxygenation during the early stages of adenine-induced chronic kidney disease.
Abstract To assess whether renal hypoxia is an early event in adenine-induced chronic kidney disease (Ad-CKD), adenine (100 mg) or its vehicle were administered to male Sprague-Dawley rats by daily oral gavage for 7 days. Kidney oxygenation was assessed by (i) blood oximetry and Clark electrode in thiobutabarbital-anesthetized rats, (ii) radiotelemetry in unanesthetized rats, and (iii) through expression of hypoxia inducible factor (HIF-1α and HIF-2α) protein. After 7 days of treatment, under anesthesia renal oxygen delivery was 51% less, while renal oxygen consumption was 65% less, in adenine-treated ...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Ullah MM, Ow CPC, Hilliard Krause LM, Evans RG Tags: Am J Physiol Renal Physiol Source Type: research

Inactivation of Tsc2 in Abcg2 Lineage Derived Cells Drives the Appearance of Polycystic Lesions and Fibrosis in the Adult Kidney.
Abstract Tuberous sclerosis complex 2, or Tuberin, is a pivotal regulator of the mechanistic target of rapamycin (mTOR) signaling pathway that controls cell survival, proliferation, growth and migration. Loss of Tsc2 function manifests in organ specific consequences, the mechanisms of which remain incompletely understood. Recent single cell analysis of kidney identified Abcg2 expression in renal proximal tubules of adult mice as well as a novel cell population. The impact in adult kidney of Tsc2 knockdown in the ATP binding cassette G2 (Abcg2) expressing lineage has not been evaluated. We engineered an inducible s...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Gewin L, Summers ME, Harral JW, Gaskill CF, Nlandu Khodo S, Neelisetty S, Sullivan TM, Hopp K, Reese JJ, Klemm DJ, Kon V, Ess KC, Shi W, Majka SM Tags: Am J Physiol Renal Physiol Source Type: research

Renovascular disease induces mitochondrial damage in swine scattered tubular cells.
Conclusions: RVD in swine is associated with a higher prevalence of STCs, but induces structural and functional alterations in STC mitochondria, which impair their reparative potency. These observations suggest a key role for mitochondria in the renal reparative capacity of STCs. PMID: 31461348 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Aghajani Nargesi A, Zhu XY, Conley SM, Woollard JR, Saadiq IM, Lerman LO, Eirin A Tags: Am J Physiol Renal Physiol Source Type: research

Urinary extracellular vesicles associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls.
Abstract Randall's plaque (RP, subepithelial calcification) appears to be an important precursor of kidney stone disease. However, RP cannot be noninvasively detected. The present study investigated candidate biomarkers associated with extracellular vesicles (EVs) in the urine of calcium stone formers (CSFs) with low (
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Chirackal RS, Jayachandran M, Wang X, Edeh S, Haskic Z, Perinpam M, Halling TM, Mehta R, Rivera ME, Lieske JC Tags: Am J Physiol Renal Physiol Source Type: research

The Renal Molecular Clock: Broken by Aging and Restored by Exercise.
Abstract The mammalian circadian clock governs physiological, endocrine, and metabolic responses coordinated in a 24h rhythmic pattern by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The SCN also dictates circadian rhythms in peripheral tissues like the kidney. The kidney has several important physiological functions including removing waste and filtering the blood, regulation of: fluid volume, blood osmolarity, blood pressure and calcium metabolism, all of which are under tight control of the molecular/circadian clock. Normal aging has a profound influence on both renal function, central and pe...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Schmitt EE, Johnson EC, Yusifova M, Bruns DR Tags: Am J Physiol Renal Physiol Source Type: research

NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway.
aacute;dy P, Offermanns S, Benyó Z Abstract Tachykinins (TKs) are involved both in the physiological regulation of urinary bladder functions and in the development of overactive bladder (OAB) syndrome. The aim of the present study was to investigate the signal transduction pathways of TKs in the detrusor muscle to provide potential pharmacological targets for the treatment of bladder dysfunctions related to enhanced TK production. Contraction force, intracellular Ca2+ concentration([Ca2+]ic) and RhoA activity were measured in mouse urinary bladder smooth muscle (UBSM). TKs and the NK2 receptor (NK2R) specif...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Dér B, Molnár PJ, Ruisanchez É, Őrsy P, Kerék M, Faragó B, Nyirády P, Offermanns S, Benyó Z Tags: Am J Physiol Renal Physiol Source Type: research

Chronic exposure to hypoxia attenuates renal injury and innate immunity activation in the remnant kidney model.
CK, Zatz R Abstract Hypoxia is thought to influence the pathogenesis of chronic kidney disease (CKD), but direct evidence that prolonged exposure to tissue hypoxia initiates or aggravates CKD is lacking. We tested this hypothesis by chronically exposing normal rats and rats with 5/6 nephrectomy (Nx) to hypoxia. In addition, we investigated whether such effect of hypoxia would involve activation of innate immunity. Adult male Munich-Wistar rats underwent Nx (n=54) or sham surgery (S, n=52). Twenty six sham (S+Nor) and 26 Nx (Nx+Nor) rats remained in normoxia, while 26 sham rats (S+Hyp) and 28 Nx rats (Nx+Hyp) were ...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Rempel LCT, Faustino VD, Foresto-Neto O, Fanelli C, Arias SCA, Moreira GCDS, Nascimento TF, Ávila VF, Malheiros DMAC, Saraiva Câmara NO, Fujihara CK, Zatz R Tags: Am J Physiol Renal Physiol Source Type: research

Glomerular permeability is not affected by heparan sulfate glycosaminoglycan deficiency in zebrafish embryos.
Abstract Proteinuria develops when specific components in the glomerular filtration barrier have impaired function. Although the precise components involved in maintaining this barrier have not been fully identified, heparan sulfate proteoglycans are believed to play an essential role in maintaining glomerular filtration. Although in situ studies showed that a loss of heparan sulfate glycosaminoglycans increases the permeability of the glomerular filtration barrier, recent studies using experimental models showed that podocyte-specific deletion of heparan sulfate glycosaminoglycan assembly does not lead to protein...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Khalil R, Lalai RA, Wiweger MI, Avramut CM, Koster AJ, Spaink HP, Bruijn JA, Hogendoorn PCW, Baelde HJ Tags: Am J Physiol Renal Physiol Source Type: research

Urinary physiology and hypoxia: a pilot study of moderate-altitude trekking effects on urodynamic indices.
This study addresses the adaptive urinary responses in four healthy adult lowlanders, comparing urodynamic indices at Kathmandu (1450 m a.s.l, K1450) and during a sojourn in Namche Bazar (3500 m a.s.l., NB3500). The urodynamic testing consisted of the cistomanometry and bladder pressure/flow measurements. Anthropometrics, electrocardiographic and peripheral capillary oxygen saturation (SpO2) data were also collected. The main findings consisted of significant reductions in the bladder power at maximum urine flow by about 30%, bladder contractility index by 13%, infused volume both at first (by 57%) and urgency sensation (b...
Source: Am J Physiol Renal P... - August 28, 2019 Category: Urology & Nephrology Authors: Verratti V, Mrakic-Sposta S, Moriggi M, Tonacci A, Bhandari S, Migliorelli D, Bajracharya A, Bondi D, Agrò EF, Cerretelli P Tags: Am J Physiol Renal Physiol Source Type: research

ROCK2 regulates TGF- β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in the mesangial cells.
ROCK2 regulates TGF-β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in the mesangial cells. Am J Physiol Renal Physiol. 2019 Jul 31;: Authors: Nagai Y, Matoba K, Kawanami D, Takeda Y, Akamine T, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K, Nishimura R Abstract The small GTPase Rho and its effector Rho-kinase are involved in the pathogenesis of diabetic kidney disease. Rho-kinase has two isoforms, ROCK1 and ROCK2. However, it remains unclear which is mainly involved in the progression of diabetic glomerulosclerosis and the regulation of profibrotic m...
Source: Am J Physiol Renal P... - July 31, 2019 Category: Urology & Nephrology Authors: Nagai Y, Matoba K, Kawanami D, Takeda Y, Akamine T, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K, Nishimura R Tags: Am J Physiol Renal Physiol Source Type: research

Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment.
In conclusion, CD73 in perivascular cells may act to suppress myofibroblast transformation and influence macrophages to promote a wound healing response. These results suggest that the purinergic signaling pathway in the kidney interstitial microenvironment orchestrates perivascular cells and macrophages to suppress inflammation and prevent progressive fibrosis. PMID: 31364375 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - July 31, 2019 Category: Urology & Nephrology Authors: Perry HM, Gorldt N, Sung SJ, Huang L, Rudnicka KP, Encarnacion IM, Bajwa A, Tanaka S, Poudel N, Yao J, Rosin DL, Schrader J, Okusa MD Tags: Am J Physiol Renal Physiol Source Type: research

MAL protein stabilizes luminal membrane PLC β3 and negatively regulates ENaC in mouse cortical collecting duct cells.
MAL protein stabilizes luminal membrane PLCβ3 and negatively regulates ENaC in mouse cortical collecting duct cells. Am J Physiol Renal Physiol. 2019 Jul 31;: Authors: Tuna KM, Liu BC, Yue Q, Ghazi ZM, Ma HP, Eaton DC, Alli AA Abstract Abnormally high epithelial sodium channel (ENaC) activity in the aldosterone sensitive distal nephron and collecting duct leads to hypertension. Mal is a lipid-raft-associated protein that has been previously shown to regulate NKCC2 (Na-K -2Cl co-transporter) and aquaporin-2 in the kidney, but it is not known whether it regulates renal ENaC. ENaC activity is positi...
Source: Am J Physiol Renal P... - July 31, 2019 Category: Urology & Nephrology Authors: Tuna KM, Liu BC, Yue Q, Ghazi ZM, Ma HP, Eaton DC, Alli AA Tags: Am J Physiol Renal Physiol Source Type: research

Targeted renal knockdown of Na+/H+ exchanger regulatory factor Sip1 produces uric acid nephrolithiasis in Drosophila.
Abstract Nephrolithiasis is one of the most common kidney diseases with poorly understood pathophysiology, but experimental study has been hindered by lack of experimentally tractable models. Drosophila melanogaster is a useful model organism for renal diseases because of genetic and functional similarities of Malpighian (renal) tubules with the human kidney. Here, we demonstrate the function of Sip1 (SRY-interacting protein 1) gene, an orthologue of human NHERF1 in Drosophila MTs, and its impact on nephrolithiasis. Abundant birefringent calculi were observed in Sip1 mutant flies, and the phenotype was also observ...
Source: Am J Physiol Renal P... - July 31, 2019 Category: Urology & Nephrology Authors: Ghimirie S, Terhzaz S, Cabrero P, Romero MF, Davies S, Dow JAT Tags: Am J Physiol Renal Physiol Source Type: research

Cellular cholesterol modifies flow mediated gene expression.
Abstract Downregulation of heme oxygenase-1 (HO1), cyclooxygenase-2 (COX2), and nitric oxide synthase-2 (NOS2) in kidney of Dahl rodents causes salt sensitivity while restoring their expression aids in sodium excretion and blood pressure reduction. Loading cholesterol into collecting duct (CD) cells represses fluid shear stress (FSS) mediated COX2 activity. Thus, we hypothesized that cholesterol represses flow responsive genes necessary to effectuate sodium excretion. To this end, CD cells were used to test whether FSS induces these genes and if cholesterol loading represses them. Mice fed either 0% or 1% choleste...
Source: Am J Physiol Renal P... - July 31, 2019 Category: Urology & Nephrology Authors: Repetti RL, Meth J, Sonubi O, Flores D, Satlin LM, Rohatgi R Tags: Am J Physiol Renal Physiol Source Type: research

Cell-free hemoglobin augments acute kidney injury during experimental sepsis.
Abstract Acute kidney injury is a common complication of severe sepsis and contributes to high mortality. The molecular mechanisms of acute kidney injury during sepsis are not fully understood. Because hemoproteins, including myoglobin and hemoglobin, mediate kidney injury during rhabdomyolysis, we hypothesized that cell-free hemoglobin would exacerbate acute kidney injury during sepsis. Sepsis was induced in mice by intraperitoneal injection of cecal slurry (CS). To mimic elevated levels of cell-free hemoglobin (CFH) observed during human sepsis, mice also received a retro-orbital injection of CFH or control. Fou...
Source: Am J Physiol Renal P... - July 31, 2019 Category: Urology & Nephrology Authors: Shaver CM, Paul MG, Putz ND, Landstreet SR, Kuck JL, Scarfe L, Skrypnyk NI, Yang H, Harrison FE, de Caestecker MP, Bastarache JA, Ware LB Tags: Am J Physiol Renal Physiol Source Type: research

Mg2+ restriction downregulates NCC through NEDD4-2 and prevents its activation by hypokalemia.
Abstract Hypomagnesemia is associated with reduced kidney function and life-threatening complications, and sustains hypokalemia. The distal convoluted tubule (DCT) determines final urinary Mg2+ excretion, and via activity of the Na+-Cl- cotransporter (NCC) also plays a key role in K+ homeostasis by metering Na+ delivery to distal segments. Little is known about the mechanisms by which plasma [Mg2+] regulates NCC activity, and how low plasma [Mg2+] and [K+] interact to modulate NCC activity. To address this we performed dietary manipulation studies in mice. Compared with normal diet, abundances of total NCC (tNCC) ...
Source: Am J Physiol Renal P... - July 31, 2019 Category: Urology & Nephrology Authors: Ferdaus MZ, Mukherjee A, Nelson JW, Blatt PJ, Miller LN, Terker A, Staub O, Lin DH, McCormick JA Tags: Am J Physiol Renal Physiol Source Type: research

p53-cyclophilin D mediates renal tubular cell apoptosis in ischemia-reperfusion-induced acute kidney injury.
Abstract Ischemia-reperfusion-induced acute kidney injury (IR-AKI) favors mitochondrial permeability transition pore (mPTP) opening and subsequent cell death. Cyclophilin D (CypD) is an essential component of the mPTP, and recent findings implicate the p53-CypD complex in cell death. To evaluate the role of p53-CypD following IR-AKI, we tested the hypothesis that the p53-CypD complex mediates renal tubular cell apoptosis in IR-AKI via mPTP opening. The expression of p53 and cleaved caspase-3 was significantly increased in rats subjected to IR-AKI compared with the normal control and sham-operated control. The unde...
Source: Am J Physiol Renal P... - July 24, 2019 Category: Urology & Nephrology Authors: Yang H, Li R, Zhang L, Zhang S, Dong W, Chen Y, Wang W, Li C, Ye Z, Zhao X, Li Z, Wu Y, Zhang M, Liu S, Dong Z, Liang X Tags: Am J Physiol Renal Physiol Source Type: research

Sex-related differences in the intratubular renin-angiotensin system (RAS) in 2-kidney 1-clip hypertensive rats.
In conclusion, the female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in intratubular nonclassic RAS(ACE2/angiotensin 1-7/MasR) and a decrease in the AT1/AT2 ratio could limit the adverse effects of classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components. PMID: 31339773 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - July 24, 2019 Category: Urology & Nephrology Authors: Lee SH, Lee YH, Jung SW, Kim DJ, Park SH, Song SJ, Jeong KH, Moon JY, Ihm CG, Lee TW, Kim JS, Sohn IS, Lee SY, Kim DO, Kim YG Tags: Am J Physiol Renal Physiol Source Type: research

In vivo measurement of kidney glomerular number and size in healthy and Os/+ mice using MRI.
Abstract The development of chronic kidney disease (CKD) is associated with the loss of functional nephrons. However, there are no methods to directly measure nephron number in living subjects. Thus, there are no methods to track the early stages of progressive CKD prior to changes in total renal function. In this work, we use cationic ferritin enhanced-magnetic resonance imaging (CFE-MRI) to enable measurements of glomerular number (Nglom) and apparent glomerular volume (aVglom) in vivo in healthy wild type (WT, n=4) and oligosyndactylism (Os/+, n=4) mice, a model of congenital renal hypoplasia leading to nephron...
Source: Am J Physiol Renal P... - July 24, 2019 Category: Urology & Nephrology Authors: Baldelomar EJ, Charlton JR, deRonde KA, Bennett KM Tags: Am J Physiol Renal Physiol Source Type: research

Human Th17 cells produce a soluble mediator that increases podocyte motility via signalling pathways which mimic PAR-1 activation.
Abstract The specific pathogenesis of idiopathic nephrotic syndrome (NS) is poorly understood and the role of immune mediators remains contentious. However, there is good evidence for the role of a circulating factor, and we recently postulated circulating proteases as candidate factors. Immunosuppressive therapy with glucocorticoids (GCs) and T cell inhibitors are widely used in the clinical treatment of NS. we hypothesised that Th17 cells produce a circulating factor that is capable of signalling to the podocyte and inducing deleterious phenotypic changes. To test this, we generated human Th17 cells from healthy...
Source: Am J Physiol Renal P... - July 24, 2019 Category: Urology & Nephrology Authors: May CJ, Welsh GI, Chesor M, Lait PJ, Schewitz-Bowers LP, Lee RW, Saleem MA Tags: Am J Physiol Renal Physiol Source Type: research

Clinical and neurohumoral associates of variation in plasma sodium in the PREVEND cohort.
In this study, we investigated the neurohumoral factors NT-proBNP and aldosterone as volume markers and copeptin as a marker for osmoregulation. Clinical associating variables of plasma sodium were age, gender and plasma glucose. Furthermore, plasma sodium levels were associated with log2 copeptin (males: st. β=0.18, P
Source: Am J Physiol Renal P... - July 24, 2019 Category: Urology & Nephrology Authors: Hessels NR, van den Bosch JJON, van Londen M, Bakker SJL, Riphagen IJ, Navis GJ Tags: Am J Physiol Renal Physiol Source Type: research

Knockout of TRPA1 exacerbates angiotensin II-induced kidney injury.
Abstract Macrophage-mediated inflammation plays a critical role in hypertensive kidney disease. Here we investigated the role of transient receptor potential ankyrin 1 (TRPA1), a sensor of inflammation, in angiotensin (Ang) II-induced renal injury. Subcutaneous infusion of Ang II (600ng/min/kg) for 28 days was used to induce hypertension and renal injury in mice. Results showed that Ang II-induced hypertensive mice have decreased renal Trpa1 expression (P
Source: Am J Physiol Renal P... - July 24, 2019 Category: Urology & Nephrology Authors: Ma S, Zhang Y, He K, Wang P, Wang D Tags: Am J Physiol Renal Physiol Source Type: research

Renal Secretion of Hydrochlorothiazide Involves Organic Anion Transporter 1/3, Organic Cation Transporter 2, and Multidrug and Toxin Extrusion Protein 2-K.
Abstract Hydrochlorothiazide (HCTZ) is the most widely used thiazide diuretic for the treatment of hypertension either alone or in combination with other antihypertensives. HCTZ is mainly cleared by the kidney via tubular secretion but the underlying molecular mechanisms are unclear. Using cells stably expressing major renal organic anion and cation transporters (hOAT1, hOAT3, hOCT2, hMATE1, and hMATE2-K), we found that HCTZ interacted with both organic cation and anion transporters. Uptake studies further showed that HCTZ is transported by hOAT1, hOAT3, hOCT2, and hMATE2-K, but not by hMATE1. Detailed kinetic ana...
Source: Am J Physiol Renal P... - July 19, 2019 Category: Urology & Nephrology Authors: Yin J, Wagner DJ, Prasad B, Isoherranen N, Thummel KE, Wang J Tags: Am J Physiol Renal Physiol Source Type: research

Krt5+ Urothelial Cells are Developmental and Tissue Repair Progenitors in the Kidney.
In this study, we traced the origins of adult Upk+ RUCs during normal development and in response to UTO. Fate mapping analysis demonstrates that adult Upk+ RUCs derive from embryonic and neonatal Krt5+ RUCs, whereas Krt5+ RUCs lose this progenitor capacity and become lineage restricted by postnatal day (P)14. However, in response to UTO, P14 labeled adult Krt5+ RUCs break their lineage restriction and robustly differentiate into Upk+ RUCs. Thus, Krt5+ RUCs drive renal urothelial formation during normal ontogeny and following UTO by differentiating into Upk+ RUCs in a temporally restricted manner. PMID: 31322419 [PubM...
Source: Am J Physiol Renal P... - July 19, 2019 Category: Urology & Nephrology Authors: Jackson AR, Hoff ML, Li B, Ching CB, McHugh KM, Becknell B Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +19 new citations
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2019/07/17PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - July 17, 2019 Category: Urology & Nephrology Tags: Report Source Type: research

Am J Physiol Renal Physiol; +57 new citations
57 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2019/07/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - July 12, 2019 Category: Urology & Nephrology Tags: Report Source Type: research

Profiling histone modifications in the normal mouse kidney and after unilateral ureteric obstruction.
In this study, we hypothesised that unilateral ureteric obstruction (UUO), a widely used model of tubulointerstitial injury, would be associated with a distinct pattern of histone (H) modifications (marks) in the kidney. Mass spectrometry (MS) was used to profile 63 different histone marks in normal mouse kidney and those after 10 days of UUO. A subsequent histochemical analysis further examined examples of specific marks that changed significantly after UUO, for which antisera are available. Histone marks were much more widely distributed and abundant in the normal kidney than usually appreciated. Although aggregate analy...
Source: Am J Physiol Renal P... - July 3, 2019 Category: Urology & Nephrology Authors: Hewitson TD, Holt SG, Samuel CS, Wigg B, Smith ER Tags: Am J Physiol Renal Physiol Source Type: research

Mitochondrial activity contributes to impaired renal metabolic homeostasis and renal pathology in STZ-induced diabetic mice.
Abstract Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide while the efficacy of current therapeutic strategies on DN remains unsatisfactory. Recent researches reported the involvement of metabolic re-arrangement in the pathological process of DN, and of all the disturbances in metabolism, mitochondria serve as key regulatory hubs. In the present study, high-resolution mass spectrometry-based none-target metabolomics was employed to uncover the metabolic characteristics of early diabetic kidney with or without the inhibition of mitochondrial activity. At first, we observed a ...
Source: Am J Physiol Renal P... - July 3, 2019 Category: Urology & Nephrology Authors: Wu M, Li S, Yu X, Chen W, Ma H, Shao C, Zhang Y, Zhang A, Huang S, Jia Z Tags: Am J Physiol Renal Physiol Source Type: research

Sex Differences in Diabetes and Kidney Disease: Mechanisms and Consequences.
Abstract Type 1 and Type 2 diabetes, along with its accompanying hyperglycemia, is associated with a multitude of comorbidities including the development of diabetic kidney disease. While the hallmarks of these metabolic disorders have been well-characterized in population and animal studies, it is becoming increasingly apparent that diabetes manifests itself differently in men and women. This review summarizes the recent diabetic literature with a focus on known sex differences in clinical and preclinical studies. It explores the physiological differences of glucose handling and the development of diabetes betwee...
Source: Am J Physiol Renal P... - June 26, 2019 Category: Urology & Nephrology Authors: Shepard BD Tags: Am J Physiol Renal Physiol Source Type: research

The contribution of collecting duct NOS1 to the concentrating mechanisms in male and female mice.
In conclusion CD NOS1 plays only a minor role in urine concentrating mechanisms. PMID: 31241990 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 26, 2019 Category: Urology & Nephrology Authors: Mendoza LD, Hyndman KA Tags: Am J Physiol Renal Physiol Source Type: research

In human nephrectomy specimens, the kidney level of tubular transport proteins does not correlate with their abundance in urinary extracellular vesicles.
sen P Abstract Human urinary extracellular vesicles (uEVs) contain proteins from all nephron segments. An assumption for years has been that uEVs might provide a non-invasive liquid biopsy that reflect physiological regulation of transporter protein expression in human. We hypothesized that protein abundance in human kidney tissue and uEV are directly related and tested this in paired collections of nephrectomy tissue and urine sample from 12 patients. Kidney tissue was fractioned into total kidney protein, crude membrane (plasma membrane and large intracellular vesicles) and intracellular vesicle enriched fractio...
Source: Am J Physiol Renal P... - June 26, 2019 Category: Urology & Nephrology Authors: Sabaratnam R, Geertsen L, Skjødt K, Hojlund K, Dimke H, Lund L, Svenningsen P Tags: Am J Physiol Renal Physiol Source Type: research

Spironolactone reduces oxidative stress in living donor kidney transplantation: a randomized controlled trial.
In conclusion, spironolactone reduces the acute increase in urinary oxidative stress in living-donor KT recipients. PMID: 31241992 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 26, 2019 Category: Urology & Nephrology Authors: Morales-Buenrostro LE, Ortega Trejo JA, Pérez-Villalva R, Marino LA, Gonzalez Bobadilla Y, Juarez H, Zamora Mejia FM, Gonzalez N, Espinoza R, Barrera-Chimal J, Bobadilla NA Tags: Am J Physiol Renal Physiol Source Type: research

Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through induction of Tollip and negative regulation of IRAK-1.
Abstract LPS inhibits HCO3- absorption in the medullary thick ascending limb (MTAL) through a TLR4-MyD88-ERK pathway that is upregulated by sepsis. Pretreatment with the nontoxic immunomodulator monophosphoryl lipid A (MPLA) prevents inhibition by LPS through activation of a TLR4-TRIF-PI3K pathway that prevents LPS-induced ERK activation. Here, we identify molecular mechanisms that underlie the protective inhibitory interaction between the MPLA-PI3K and LPS-ERK pathways. Treatment of mouse MTALs with LPS in vitro increased phosphorylation of interleukin-1 receptor-associated kinase (IRAK)-1, a critical mediator of...
Source: Am J Physiol Renal P... - June 26, 2019 Category: Urology & Nephrology Authors: Watts BA, Tamayo EH, Sherwood ER, Good DW Tags: Am J Physiol Renal Physiol Source Type: research

Smooth muscle-specific deletion of MnSOD exacerbates diabetes-induced bladder dysfunction in mice.
Abstract Bladder dysfunction in diabetes progresses gradually over time. However, the mechanisms of the development are not clear. We test the hypothesis that oxidative stress plays a key role in the development of diabetic bladder dysfunction, using an inducible smooth muscle (SM)-specific Sod2 gene knockout (SM-Sod2 KO) mouse model. Eight-week-old male Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice and wild-type mice were assigned to diabetic or control groups. 4-hydroxytamoxifen was injected into Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice to activate CreERT2-mediated deletion of Sod2. Diabetes was induced by injection of str...
Source: Am J Physiol Renal P... - June 26, 2019 Category: Urology & Nephrology Authors: Elrashidy RA, Kavran M, Asker ME, Mohamed HE, Daneshgari F, Liu G Tags: Am J Physiol Renal Physiol Source Type: research