Targeting STAT3 Signaling in Kidney Disease.
Abstract The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is a multifaceted transduction system which regulates cellular responses to incoming signaling ligands. Signal transducer and activator of transcription 3 (STAT3) is a central member of the JAK/STAT signaling cascade and has long been recognized for its increased transcriptional activity in cancers and autoimmune disorders, but has only recently been in the spotlight for its role in the progression of kidney disease. While genetic knockout and manipulation studies have demonstrated the salutary benefits of inh...
Source: Am J Physiol Renal P... - April 3, 2019 Category: Urology & Nephrology Authors: Pace J, Paladugu P, Das B, He JC, Mallipattu SK Tags: Am J Physiol Renal Physiol Source Type: research

The Role of GM-CSF in a Mouse Model of Experimental Autoimmune prostatitis.
Abstract The etiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the development of autoimmune and inflammatory diseases. Here, we investigated the expression and function of GM-CSF in CP/CPPS patients and in a mouse model of Experimental Autoimmune prostatitis (EAP). GM-CSF mRNA levels were detected in expressed prostatic secretions samples from CP/CPPS patients and in prostate tissue from a mouse model of EAP. The expression of GM-CSF receptor in mouse prostate and dorsal roo...
Source: Am J Physiol Renal P... - April 3, 2019 Category: Urology & Nephrology Authors: Liu Y, Li Y, Liu Q, Wu Z, Cui J, Zhu K, Zhao H, Zhou C, Shi B Tags: Am J Physiol Renal Physiol Source Type: research

Cre/lox System: Cre-ating Unintended Damage.
PMID: 30943071 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - April 3, 2019 Category: Urology & Nephrology Authors: Gewin L Tags: Am J Physiol Renal Physiol Source Type: research

Elevated Serum Anion Gap in Adults with Moderate Chronic Kidney Disease Increases Risk for Progression to End Stage Renal Disease.
Abstract BACKGROUND: Acid retention associated with reduced GFR exacerbates nephropathy progression in partial nephrectomy models of CKD and might be reflected in CKD patients with reduced eGFR by increased anion gap (AG). METHODS: We explored the presence of AG and its association with CKD in 14,924 adults, aged ≥20 years and eGFR≥15ml/min/1.73m2, enrolled in the National Health and Nutrition Examination Survey III, 1988-1994 using multivariable regression analysis. The model was adjusted for socio-demographic characteristics, diabetes, and hypertension. We further examined the association between AG a...
Source: Am J Physiol Renal P... - March 25, 2019 Category: Urology & Nephrology Authors: Banerjee T, Crews D, Wesson DE, McCulloch C, Johansen K, Saydah S, Rios Burrows N, Saran R, Gillespie B, Bragg-Gresham J, Powe NR Tags: Am J Physiol Renal Physiol Source Type: research

Functional changes in low and high threshold afferents in obstruction-induced bladder overactivity.
Abstract Neural mechanisms of lower urinary tract symptoms in obstruction-induced bladder overactivity remain unclear. We made the first single unit recordings from the different type of spinal afferents to determine the effects of bladder outlet obstruction in guinea pigs. A model of gradual bladder outlet obstruction in male guinea pigs was used to produce overactive bladder. Conscious voiding was assessed in metabolic cages, micturition was recorded in anaesthetized guinea pigs in vivo. Single unit extracellular recordings were made ex vivo from spinal afferent nerves in flat sheet preparations of the bladder. ...
Source: Am J Physiol Renal P... - March 25, 2019 Category: Urology & Nephrology Authors: Zagorodnyuk VP, Keightley LJ, Brookes SJH, Spencer NJ, Costa MC, Nicholas SJ Tags: Am J Physiol Renal Physiol Source Type: research

Heritability and individuality of the plasma sodium concentration: a twin study in the US Veteran population.
Abstract Little is known about the population genetics of water balance. A recent meta-GWAS on plasma sodium concentration identified novel loci of high biological plausibility, yet heritability was never convincingly shown in European ancestry. The present analysis linked the Vietnam Era Twin Registry with the Department of Veterans Affairs VistA database. Participants (n = 2370; 59.6% monozygotic and 40.4% dizygotic twins) had a median of 7 (IQR: 3, 14) plasma sodium determinations between October 1999 and March 2017. Heritability of the mean plasma sodium concentration among all twins was 0.41 (0.35 - 0.46; 95%...
Source: Am J Physiol Renal P... - March 25, 2019 Category: Urology & Nephrology Authors: Timmons AK, Korpak AM, Tan J, Moore KP, Liu CH, Forsberg CW, Goldberg J, Smith NL, Cohen DM Tags: Am J Physiol Renal Physiol Source Type: research

Renal Sodium Excretion Consequent to Pharmacogenetic Activation of Gq-DREADD in Principal Cells.
Abstract Stimulation of Gq-coupled metabotropic P2Y2 receptors decrease the activity of ENaC in renal principal cells of the distal nephron. The physiological consequences of disrupting P2Y2 receptor signaling in the P2Y2 receptor knockout mouse are decreased sodium excretion and increased arterial blood pressure. However, because of the global nature of this knockout model, the quantitative contribution of ENaC and the distal nephron versus that of upstream renal vascular and tubular elements to changes in urinary excretion and arterial blood pressure are obscure. Moreover, it is uncertain whether stimulation of ...
Source: Am J Physiol Renal P... - February 6, 2019 Category: Urology & Nephrology Authors: Mironova E, Suliman F, Stockand JD Tags: Am J Physiol Renal Physiol Source Type: research

Dietary restriction of iron availability attenuates UPEC pathogenesis in a mouse model of urinary tract infection.
Abstract Iron is a critical nutrient required by hosts and pathogens. Uropathogenic Escherichia coli (UPEC), the principal causative agent of urinary tract infections (UTIs), chelate iron for their survival and persistence. Here, we demonstrate that dietary modulation of iron availability limits UPEC burden in a mouse model of UTI. Mice on a low iron diet exhibit reduced systemic and bladder mucosal iron availability, harbor significantly lower bacterial burden, concomitant with dampened inflammation. Hepcidin is a master regulator of iron that controls iron-dependent UPEC intracellular growth. Hepcidin deficient ...
Source: Am J Physiol Renal P... - February 6, 2019 Category: Urology & Nephrology Authors: Bauckman KA, Matsuda R, Higgins CB, DeBosch BJ, Wang C, Mysorekar IU Tags: Am J Physiol Renal Physiol Source Type: research

Endogenous IL-22 is dispensable for experimental glomerulonephritis.
In conclusion, we show here that endogenous IL-22 expression is redundant in different forms of glomerular injury, indicating that the IL-22-directed therapies that are being tested in various human diseases might not affect the kidney in patients with glomerular disease. PMID: 30724106 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 6, 2019 Category: Urology & Nephrology Authors: Gnirck AC, Wunderlich M, Becker M, Xiong T, Weinert E, Meyer-Schwesinger C, Dumoutier L, Renauld JC, Huber S, Panzer U, Turner JE Tags: Am J Physiol Renal Physiol Source Type: research

Endothelial Cell-Specific Collagen IV α3 Expression Does not Rescue Alport Syndrome in Col4a3-/- Mice.
Endothelial Cell-Specific Collagen IV α3 Expression Does not Rescue Alport Syndrome in Col4a3-/- Mice. Am J Physiol Renal Physiol. 2019 Feb 06;: Authors: Funk SD, Bayer RH, Miner JH Abstract The glomerular basement membrane (GBM) is a critical component of the kidney's blood filtration barrier. Alport syndrome, a hereditary disease leading to kidney failure, is caused by the loss or dysfunction of the GBM's major type IV collagen (COL4) isoform, α3α4α5. The constituent COL4 achains assemble into heterotrimers in the endoplasmic reticulum prior to secretion into the extracellula...
Source: Am J Physiol Renal P... - February 6, 2019 Category: Urology & Nephrology Authors: Funk SD, Bayer RH, Miner JH Tags: Am J Physiol Renal Physiol Source Type: research

Acute kidney injury induces dramatic p21 up-regulation via a novel, glucocorticoid- activated, p53 independent, pathway.
ACUTE KIDNEY INJURY INDUCES DRAMATIC P21 UP-REGULATION VIA A NOVEL, GLUCOCORTICOID- ACTIVATED, P53 INDEPENDENT, PATHWAY. Am J Physiol Renal Physiol. 2019 Jan 30;: Authors: Zager RA, Johnson AC Abstract P21, a cyclin kinase inhibitor, is acutely up-regulated during AKI and exerts cytoprotective effects. A proposed mechanism is oxidant stress- induced activation of p53, the dominant p21 transcription factor. Glycerol-induced rhabdomyolysis induces profound renal oxidant stress. Hence, we studied this AKI model to determine whether p53 activation corresponds with p21 gene induction, and/or whether altern...
Source: Am J Physiol Renal P... - January 30, 2019 Category: Urology & Nephrology Authors: Zager RA, Johnson AC Tags: Am J Physiol Renal Physiol Source Type: research

Estrogen-Related Receptor α Mediates Puromycin Aminonucleoside-induced Mesangial Cell apoptosis and Inflammatory Injury.
Estrogen-Related Receptor α Mediates Puromycin Aminonucleoside-induced Mesangial Cell apoptosis and Inflammatory Injury. Am J Physiol Renal Physiol. 2019 Jan 30;: Authors: Gong W, Song J, Chen X, Li S, Yu J, Xia W, Ding G, Zhang Y, Jia Z, Zhang A, Huang S Abstract Glomerular diseases are the leading causes of chronic kidney disease and mesangial cells (MCs) were demonstrated to be involved in the pathogenesis. Puromycin aminonucleoside (PAN) is a nephrotoxic drug that induced glomerular injury with elusive mechanisms. The present study is undertaken to investigate the role of PAN in MC apoptosis...
Source: Am J Physiol Renal P... - January 30, 2019 Category: Urology & Nephrology Authors: Gong W, Song J, Chen X, Li S, Yu J, Xia W, Ding G, Zhang Y, Jia Z, Zhang A, Huang S Tags: Am J Physiol Renal Physiol Source Type: research

Lipoprotein lipase in mouse kidney: effects of nutritional status and high-fat diet.
ona G Abstract Activity of lipoprotein lipase (LPL) is high in mouse kidney, but the reason is poorly understood. The aim was to characterize localization, regulation and function of LPL in kidney of C57BL/6J mice. We found LPL mainly in proximal tubules, localized inside the tubular epithelial cells, under all conditions studied. In fed mice some LPL colocalized with the endothelial markers CD31 and GPIHBP1, and could be removed by perfusion with heparin, indicating a vascular location. The role of angiopoietin-like protein 4 (ANGPTL4) for nutritional modulation of LPL activity was studied in wild-type and Angptl...
Source: Am J Physiol Renal P... - January 30, 2019 Category: Urology & Nephrology Authors: Nyrén R, Makoveichuk E, Malla S, Kersten S, Nilsson SK, Ericsson M, Olivecrona G Tags: Am J Physiol Renal Physiol Source Type: research

Sympathetic Afferents in the Hypogastric Nerve Facilitate Nociceptive Bladder Activity in Cats.
This study in α-chloralose anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly (p
Source: Am J Physiol Renal P... - January 23, 2019 Category: Urology & Nephrology Authors: Zhang Y, Li S, Yecies T, Morgan T, Cai H, Pace N, Shen B, Wang J, Roppolo JR, de Groat WC, Tai C Tags: Am J Physiol Renal Physiol Source Type: research

Protease-activated receptor 2 exacerbates cisplatin-induced nephrotoxicity.
Abstract Acute kidney injury (AKI) is associated with hypercoagulability. Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade activate protease-activated receptor 2 (PAR2). Previously, we have shown that PAR2-mediated inflammation aggravates kidney injury in models of diabetic kidney disease and adenine-induced renal fibrosis. However, the role of PAR2 in AKI remains unclear. In order to clarify the role of PAR2, we administered cisplatin, one of the most common causal factors of AKI, to wild-type and PAR2-deficient mice. The expression levels of tissue factor and PAR2 were significantly inc...
Source: Am J Physiol Renal P... - January 23, 2019 Category: Urology & Nephrology Authors: Watanabe M, Oe Y, Sato E, Sekimoto A, Sato H, Ito S, Takahashi N Tags: Am J Physiol Renal Physiol Source Type: research

Lps removal reduces cd80-mediated albuminuria in critically ill patients with gram-negative sepsis.
This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomised to either have Coupled Plasma Filtration and Adsorption (CPFA) added to the standard care (n=35) or not (n=35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria and CD80 expression in Gram- sepsis, a swine model of LPS-induced AKI was set up. 3-hours after LPS infusion, animals were treated or not with CPFA for 6-hours. Treat...
Source: Am J Physiol Renal P... - January 23, 2019 Category: Urology & Nephrology Authors: Netti GS, Sangregorio F, Spadaccino F, Staffieri F, Crovace A, Infante B, Maiorano A, Godeas G, Castellano G, Di Palma AM, Prattichizzo C, Cotoia A, Mirabella L, Gesualdo L, Cinnella G, Stallone G, Ranieri E, Grandaliano G Tags: Am J Physiol Renal Physiol Source Type: research

Bladder urothelial BK channel activity is a critical mediator for innate immune response in urinary tract infection pathogenesis.
Abstract The open probability of calcium activated voltage gated potassium channel (BK channel) on bladder umbrella urothelial cells is increased by lipopolysaccharide (LPS). It is hypothesized that this channel's activity is important in the urothelial innate immune response during urinary tract infection (UTI). We performed in vivo studies using female C57BL/6 mice whose bladders were inoculated with lipopolysaccharide (150 μl of 1 mg/mL LPS) or uropathogenic E. coli (UPEC, UTI89), without and with intravesical BK inhibitor iberiotoxin (IBTX, 1 μM). Inflammatory biomarkers (chemokines and cytokines) were m...
Source: Am J Physiol Renal P... - January 16, 2019 Category: Urology & Nephrology Authors: Yeh J, Lu M, Alvarez-Lugo L, Chai TC Tags: Am J Physiol Renal Physiol Source Type: research

Multiparametric assessment of renal physiology in healthy volunteers using non-invasive magnetic resonance imaging.
In conclusion, non-invasive MRI provides useful tools to evaluate intra renal differences in blood flow, perfusion, diffusion, oxygenation and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our current understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease. PMID: 30648907 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 16, 2019 Category: Urology & Nephrology Authors: Eckerbom P, Hansell P, Cox EF, Buchanan C, Weis J, Palm F, Francis ST, Liss P Tags: Am J Physiol Renal Physiol Source Type: research

Renal Cortical Oxygen Tension is Decreased Following Exposure to Long-term but not Short-term Intermittent Hypoxia in the Rat.
Abstract Chronic kidney disease (CKD) occurs in more than 50% of patients with obstructive sleep apnea (OSA). However, the impact of intermittent hypoxia (IH) on renal function and oxygen homeostasis is unclear. Male Sprague Dawley rats were exposed to IH (270 secs at 21% O2; 90 secs hypoxia, 6.5% O2 at nadir) for 4 h (AIH) or to chronic IH (CIH) for 8h/day for 2 weeks. Animals were anesthetized and surgically prepared for the measurement of mean arterial pressure (MAP), and left renal excretory function, renal blood flow (RBF), and renal oxygen tension (PO2). AIH had no effect on MAP (123±14 versus (v) 129...
Source: Am J Physiol Renal P... - January 16, 2019 Category: Urology & Nephrology Authors: O'Neill J, Jasionek G, Drummond SE, Brett O, Lucking EF, Abdulla MA, O'Halloran KD Tags: Am J Physiol Renal Physiol Source Type: research

The role of regulatory T cells in Experimental Autoimmune Glomerulonephritis.
In conclusion, our results indicate that in anti-GBM disease Treg cells restrict the induction of autoimmunity against α3(IV)NC1. However, Treg cells are inefficient in preventing crescentic GN after autoimmunity has established. PMID: 30648909 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 16, 2019 Category: Urology & Nephrology Authors: Klinge S, Yan K, Reimers D, Brede KM, Schmid J, Paust HJ, Krebs CF, Panzer U, Hopfer H, Mittrücker HW Tags: Am J Physiol Renal Physiol Source Type: research

Blockade of ERK1/2 by U0126 alleviates uric acid induced EMT and tubular cell injury in the rats with hyperuricemic nephropathy.
In this study, we showed that hyperuricemic injury induced EMT as characterized by down-regulation of E-cadherin and up-regulation of Vimentin and Snail1 in a rat model of HN. This was coincident with epithelial cells arrested at the G2/M phase of cell cycle, activation of Notch1/Jagged-1 and Wnt/β-catenin signaling pathways, and upregulation of matrix metalloproteinases 2 (MMP2) and MMP9. Administration of U0126, a selective inhibitor of ERK1/2, blocked all these responses. U0126 was also effective in inhibiting renal tubular cell injury as shown by decreased expression of lipocalin-2 (Lcn2) and kidney injury molecul...
Source: Am J Physiol Renal P... - January 16, 2019 Category: Urology & Nephrology Authors: Tao M, Shi Y, Tang L, Wang Y, Fang L, Jiang W, Lin T, Qiu A, Zhuang S, Liu N Tags: Am J Physiol Renal Physiol Source Type: research

Inhibition of 5-Lipoxygenase Decreases Renal Fibrosis and Progression of Chronic Kidney Disease.
Abstract In inflammatory diseases, the 5-lipoxygenase (5-LO) pathway contributes to epithelial damage and fibrosis by catalyzing the production of leukotrienes. Antagonists of the 5-LO pathway are currently approved for use in patients and are well tolerated. We found that expression of 5-LO is strongly induced in three models of chronic kidney disease, unilateral ureteral obstruction (UUO), folate nephropathy, and an orthologous mouse model of polycystic kidney disease. Immunohistochemistry showed that macrophages are the dominant source of 5-LO. Zileuton, an FDA-approved antagonist of 5-LO, significantly reduced...
Source: Am J Physiol Renal P... - January 16, 2019 Category: Urology & Nephrology Authors: Montford JR, Bauer C, Dobrinskikh E, Hopp K, Levi M, Weiser-Evans MC, Nemenoff RA, Furgeson SB Tags: Am J Physiol Renal Physiol Source Type: research

Zinc Deficiency Induces Hypertension by Promoting Renal Sodium Reabsorption.
This study links dysregulated renal Na+ handling to ZnD-induced hypertension. Furthermore, NCC is identified as a novel mechanism by which Zn2+ regulates BP. Understanding the mechanisms of ZnD-induced BP dysregulation may have important therapeutic impact on hypertension. PMID: 30649891 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 16, 2019 Category: Urology & Nephrology Authors: Williams CR, Mistry M, Cheriyan AM, Williams JM, Naraine MK, Ellis CL, Mallick R, Mistry AC, Gooch JL, Ko B, Cai H, Hoover RS Tags: Am J Physiol Renal Physiol Source Type: research

Iron handling by the human kidney: Glomerular filtration and tubular reabsorption both contribute to urinary iron excretion.
CONCLUSION: Our explorative study demonstrates that both glomerular filtration of elevated plasma iron levels and insufficient tubular iron reabsorption could increase urinary iron excretion and cause renal injury. PMID: 30623722 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 9, 2019 Category: Urology & Nephrology Authors: van Raaij SE, Rennings AJ, Biemond BJ, Schols SE, Wiegerinck ET, Roelofs HM, Hoorn EJ, Walsh SB, Nijenhuis T, Swinkels DW, Van Swelm R Tags: Am J Physiol Renal Physiol Source Type: research

Identification of NFAT5 as a transcriptional regulator of the EDN1gene in collecting duct.
Abstract The inner medullary collecting duct (IMCD) produces very high levels of endothelin-1 (ET-1) that acts as an autocrine inhibitor of IMCD Na+and water reabsorption. Recent studies suggest that IMCD ET-1 production is enhanced by extracellular hypertonicity as can occur during high salt intake. While NFAT5 has been implicated in the IMCD ET-1 hypertonicity response, no studies in any cell type have identified NFAT5 as a transcriptional regulator of the EDN1gene; the currently study examined this using a mouse IMCD cell line (IMCD3). Media hypertonicity increased IMCD3 ET-1 mRNA in a dose- and time-dependent ...
Source: Am J Physiol Renal P... - January 9, 2019 Category: Urology & Nephrology Authors: Lakshmipathi J, Wheatley W, Kumar A, Mercenne G, Rodan AR, Kohan DE Tags: Am J Physiol Renal Physiol Source Type: research

TGF- β1 modifies histone acetylation and acetyl-coenzyme A metabolism in renal myofibroblasts.
In conclusion, TGF-b1 produces a metabolic reprogramming in renal fibroblasts, with less H3 acetylation through reduced acetylation, increased deacetylation and changes in carbon availability. Our results suggest that acetyl-CoA availability predominates over HAT and HDAC activity as a key determinant of H3 acetylation in response to TGF-b1. PMID: 30623724 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 9, 2019 Category: Urology & Nephrology Authors: Smith ER, Wigg B, Holt S, Hewitson TD Tags: Am J Physiol Renal Physiol Source Type: research

Adenine acts in the kidney as a signaling factor and causes salt- and water-losing nephropathy: Early mechanism of adenine-induced renal injury.
In conclusion, adenine acts on renal tubules as a signaling molecule and causes nephrogenic diabetes insipidus with salt wasting, at least, by directly interfering with AVP V2 receptor signaling with subsequent downregulation of NKCC2 and AQP2 in the kidney. The combination of renal fluid loss and decreased food intake with subsequent massive volume depletion likely plays an important role in the development of early pre-renal failure that progresses to chronic kidney disease in long-term adenine feeding. PMID: 30623725 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 9, 2019 Category: Urology & Nephrology Authors: Dos Santos IF, Sheriff S, Amlal S, Ahmed RP, Thakar CV, Amlal H Tags: Am J Physiol Renal Physiol Source Type: research

Uropathogenic Escherichia coli-Induced Fibrosis, leading to Lower Urinary Tract Symptoms, is associated with Type-2 cytokine signaling.
This study showed that while prostatic infection of CP1 causes the development of chronic tactile allodynia in NOD/ShiltJ (NOD) but not C57BL/6 (B6) mice, both mice developed evidence of prostate inflammation, prostate fibrosis, and urinary dysfunction. Fibrosis was confirmed by the upregulation of fibrosis associated messenger RNAs (mRNAs), alpha smooth muscle actin immunohistochemistry, and collagen staining with picrosirus red. These findings were mainly focused in the dorsolateral lobes of the prostate. Both mouse strains also developed smaller, more frequent voiding patterns, post-infection, examined via cystometry. B...
Source: Am J Physiol Renal P... - January 9, 2019 Category: Urology & Nephrology Authors: Bell-Cohn A, Mazur DJ, Hall CC, Schaeffer AJ, Thumbikat P Tags: Am J Physiol Renal Physiol Source Type: research

Kir4.1/5.1 in the DCT plays a role in the regulation of renal K+ excretion.
Abstract The aim of this mini review is to provide an overview regarding the role of inwardly-rectifying potassium channel 4.1 (Kir4.1)/Kir5.1 in regulating renal K+ excretion. Deletion of Kir4.1 in the kidney inhibited thiazide-sensitive NaCl cotransporter (NCC) activity in the distal convoluted tubule (DCT) and slightly suppressed Na-K-2Cl cotransporter (NKCC2) function in the thick ascending limb (TAL). Moreover, increased dietary K+ intake inhibited, whereas decreased dietary K+ intake stimulated, the basolateral potassium channel (a Kir4.1/Kir5.1 heterotetramer) in the DCT. The alteration of the basolateral p...
Source: Am J Physiol Renal P... - January 9, 2019 Category: Urology & Nephrology Authors: Su XT, Ellison DH, Wang WH Tags: Am J Physiol Renal Physiol Source Type: research

Heterozygous Pkhd1C642* mice develop cystic liver disease and proximal tubule ectasia that mimics radiographic signs of medullary sponge kidney.
Abstract Heterozygosity for human PKHD1 mutations was recently associated with cystic liver disease and radiographic findings resembling medullary sponge kidney (MSK). However, the relevance of these associations has been tempered by a lack of cystic liver or renal disease in heterozygous mice carrying Pkhd1 gene trap or exon deletions. To determine whether heterozygosity for a smaller Pkhd1 defect can trigger cystic renal disease in mice, we generated and characterized mice with the predicted truncating Pkhd1C642* mutation in a region corresponding to the middle of exon 20 cluster of five truncating human mutatio...
Source: Am J Physiol Renal P... - January 2, 2019 Category: Urology & Nephrology Authors: Shan D, Rezonzew G, Mullen S, Roye R, Zhou J, Chumley P, Revell DZ, Challa AK, Kim H, Lockhart ME, Schoeb TR, Croyle MJ, Kesterson RA, Yoder BK, Guay-Woodford LM, Mrug M Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2018 Dec 01;315(6):F1885 Authors: PMID: 30540507 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - December 1, 2018 Category: Urology & Nephrology Tags: Am J Physiol Renal Physiol Source Type: research

Reply to Wolf: Osmotically inactive sodium and potassium storage.
PMID: 30540508 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - December 1, 2018 Category: Urology & Nephrology Authors: Nguyen MK, Nguyen MK, Nguyen DS Tags: Am J Physiol Renal Physiol Source Type: research

Tracking renal injury using multiparametric MRI.
PMID: 30512997 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - December 1, 2018 Category: Urology & Nephrology Authors: Ma S, Qian C, Wang DH Tags: Am J Physiol Renal Physiol Source Type: research

Electrically stimulated acupuncture increases renal blood flow through exosome-carried miR-181.
This study provides important new insights about the mechanism(s) by which acupuncture may regulation of muscle-organ cross talk through exosome-derived microRNA. PMID: 30481066 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 29, 2018 Category: Urology & Nephrology Authors: Klein JD, Wang XH Tags: Am J Physiol Renal Physiol Source Type: research

Multiphoton imaging reveals axial differences in metabolic autofluorescence signals along the kidney proximal tubule.
Abstract Kidney proximal tubules (PTs) are densely packed with mitochondria, and defects in mitochondrial function are implicated in many kidney diseases. However, little is known about intrinsic mitochondrial function within PT cells. Here, using intravital multiphoton microscopy and live slices of mouse kidney cortex, we show that autofluorescence signals provide important functional readouts of redox state and substrate metabolism and that there are striking axial differences in signals along the PT. Mitochondrial NAD(P)H intensity was similar in both PT segment (S)1 and S2 and was sensitive to changes in respi...
Source: Am J Physiol Renal P... - November 29, 2018 Category: Urology & Nephrology Authors: Bugarski M, Martins JR, Haenni D, Hall AM Tags: Am J Physiol Renal Physiol Source Type: research

ADAMTS13 protects mice against renal ischemia/reperfusion injury by reducing inflammation and improving endothelial function.
EY Abstract Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia/reperfusion injury (IR) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation and microvascular endothelial fun...
Source: Am J Physiol Renal P... - November 21, 2018 Category: Urology & Nephrology Authors: Zhou S, Jiang S, Guo J, Xu N, Wang Q, Zhang G, Zhao L, Zhou Q, Fu X, Li L, Patzak A, Hultström M, Lai EY Tags: Am J Physiol Renal Physiol Source Type: research

Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts.
In conclusion, hypertonicity regulates water reabsorption by activating PKC. Hypertonicity-stimulated water reabsorption by PKC may be related to the decrease in endocytosis of AQP2. AMPK activation promotes water reabsorption, but the mechanism remains to be determined. PKC and AMPK do not appear to act synergistically to regulate water reabsorption. PMID: 30427219 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 14, 2018 Category: Urology & Nephrology Authors: Liwang J, Ruiz JA, LaRocque LM, Rianto F, Ma F, Wang Y Tags: Am J Physiol Renal Physiol Source Type: research

Characterization of renal NaCl and oxalate transport in Slc26a6-/- mice.
Abstract The apical membrane chloride-oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in microperfused tubules. The present study is directed at characterizing the role of SLC26A6 in NaCl homeostasis in vivo under physiological conditions. Free-flow micropuncture studies revealed that volume and chloride absorption were similar in surface proximal tubules of wild-type and Slc26a6-/- mice. Moreover, the increments in urine flow rate and sodium excretion following thiazide and furosemide infusion were identical in wild-type and Slc26a6-/- mice, indica...
Source: Am J Physiol Renal P... - November 14, 2018 Category: Urology & Nephrology Authors: Knauf F, Velazquez H, Pfann V, Jiang Z, Aronson PS Tags: Am J Physiol Renal Physiol Source Type: research

Human Serum Albumin Redox State is Associated with Decreased Renal Function in a Community-Dwelling Population.
Abstract The redox state of human serum albumin (HSA) has attracted interest as a possible biomarker for oxidative stress (OS) in humans. Although previous studies on this topic have taken only clinical settings into consideration, evidence of its efficacy in nonclinical settings remains to be established. The present study aimed to examine and validate the relationship between HSA redox state and renal function in a rural Japanese population. We analyzed two independent datasets from health check-up programs conducted in 2013 and 2016: one for discovery (n = 267) and the other for replication (n = 367). The fract...
Source: Am J Physiol Renal P... - November 14, 2018 Category: Urology & Nephrology Authors: Fujii R, Ueyama J, Kanno T, Suzuki K, Hamajima N, Wakai K, Hasegawa Y, Kondo T Tags: Am J Physiol Renal Physiol Source Type: research

SGLT2 inhibition and renal urate excretion: the role of luminal glucose, GLUT9 and URAT1.
Abstract Inhibitors of the sodium-glucose cotransporter SGLT2 enhance urinary glucose and urate excretion and lower plasma urate levels. The mechanisms remain unclear, but a role for enhanced glucose in the tubular fluid has been proposed, which may interact with tubular urate transporters like GLUT9 or URAT1. Studies were performed in non-diabetic mice using the SGLT2 inhibitor canagliflozin and gene targeted mice lacking the urate transporter GLUT9 in the tubule or mice with whole body knockout of SGLT2, SGLT1, or URAT1. Renal urate handling was assessed by analyzing urate in spontaneous plasma and urine samples...
Source: Am J Physiol Renal P... - November 14, 2018 Category: Urology & Nephrology Authors: Novikov A, Fu Y, Huang W, Freeman B, Patel R, van Ginkel C, Koepsell H, Busslinger M, Onishi A, Nespoux J, Vallon V Tags: Am J Physiol Renal Physiol Source Type: research

Identifying Cystogenic Paracrine Signaling Molecules in Cyst Fluid of Patients with Polycystic Kidney Disease.
In conclusion, both kidney and liver cyst fluids contain paracrine signaling molecules that drive cyst formation. Using size exclusion chromatography and mass spectrometry, we procured a candidate list for future studies. Ultimately, cystogenic paracrine signaling molecules may be targeted to abrogate cystogenesis in ADPKD. PMID: 30403162 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 7, 2018 Category: Urology & Nephrology Authors: Kenter A, Van Rossum-Fikkert SE, Salih M, Verhagen PCMS, Van Leenders GJLH, Demmers JAA, Jansen G, Gribnau JH, Zietse R, Hoorn EJ Tags: Am J Physiol Renal Physiol Source Type: research

Renal release of Ac-SDKP is part of an antifibrotic peptidergic system in the kidney.
Abstract The anti-fibrotic peptide Ac-SDKP is released from Thymosin β4 (Tβ4) by meprin-α and prolyl oligopeptidase (POP) enzymes and is hydrolyzed by angiotensin-converting enzyme (ACE). Ac-SDKP is present in urine however it is not clear if de novo tubular release exists or the glomerular filtration is the main source. We hypothesized that Ac-SDKP is released in the lumen of the nephron and that it has an anti-fibrotic effect. We determined the presence of Tβ4, meprin-α, and POP in the kidneys of Sprague-Dawley rats. The stop-flow technique was used to evaluate Ac-SDKP formation in dif...
Source: Am J Physiol Renal P... - November 7, 2018 Category: Urology & Nephrology Authors: Romero CA, Kumar N, Nakagawa P, Worou ME, Liao TD, Peterson EL, Carretero OA Tags: Am J Physiol Renal Physiol Source Type: research

STAT1 regulates macrophage number and phenotype and prevents renal fibrosis after ischemia/reperfusion injury.
Abstract Renal ischemia/reperfusion injury (IRI) leads to acute kidney injury or delayed allograft function which predisposes to fibrosis in the native kidney or kidney transplant. Here we investigated the role of the signal transducer and activator of transcription 1 (STAT1) in inflammatory responses following renal IRI. Our study showed that a subsequent stimulation of Janus Kinase 2/STAT1 and toll-like receptor 4 pathways led to greater STAT1 activation followed by increased cytokine transcription compared to single-pathway stimulation in murine renal tubular cells. Moreover, we observed increased activation of...
Source: Am J Physiol Renal P... - November 7, 2018 Category: Urology & Nephrology Authors: Kemmner S, Bachmann Q, Steiger S, Lorenz G, Honarpisheh M, Foresto-Neto O, Wang S, Carbajo-Lozoya J, Alt V, Schulte C, Chmielewski S, Bluyssen HAR, Heemann U, Baumann M, Lech M, Schmaderer C Tags: Am J Physiol Renal Physiol Source Type: research

SIRT1-mediated HMGB1 deacetylation suppresses sepsis-associated acute kidney injury.
Abstract Sepsis is the leading cause of death in the intensive care unit and continues to lack effective treatment. It is widely accepted that HMGB1 is a key inflammatory mediator in the pathogenesis of sepsis. Moreover, some studies indicate that the functions of HMGB1 depend on its molecular localization and post-translational modifications. Our previous study confirms that SIRT1, a type III deacetylase, can ameliorate sepsis-associated acute kidney injury (SA-AKI). We explored the effect and mechanism of SIRT1 on HMGB1 using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and LPS-treated human...
Source: Am J Physiol Renal P... - October 31, 2018 Category: Urology & Nephrology Authors: Wei S, Gao Y, Dai X, Fu W, Cai S, Fang H, Zeng Z, Chen Z Tags: Am J Physiol Renal Physiol Source Type: research

The determinants, biomarkers and consequences of microvascular injury in kidney transplant recipients.
nal H Abstract Independent of the initial cause of kidney disease, microvascular injury to the peritubular capillary network appears to play a central role in the development of interstitial fibrosis in both native and transplanted kidney disease. This association is explained by mechanisms such as the upregulation of pro-fibrotic genes and epigenetic changes induced by hypoxia, capillary leakage, endothelial and pericyte transition to interstitial fibroblasts as well modifications in the secretome of endothelial cells. Alloimmune injury due to antibody-mediated rejection and ischemia-reperfusion injury are the tw...
Source: Am J Physiol Renal P... - October 31, 2018 Category: Urology & Nephrology Authors: Doreille A, Dieudé M, Cardinal H Tags: Am J Physiol Renal Physiol Source Type: research

(Pro)Renin Receptor Contributes to Pregnancy-Induced Sodium-Water Retention in Rats via Activation of Intrarenal RAAS and α-ENaC.
The objective of the present study was to test potential roles of renal PRR and intrarenal RAAS in physiological status of late pregnancy. Late pregnant Sprague-Dawley rats were studied either 19-21 days after sperm was observed in vaginal smears. Experiments were performed on age-matched virgin rats, and late pregnant rats treated with specific PRR inhibitor PRO20 (700μg/kg/day sc for 14 days, 3 times a day for every 8 h) or vehicle. The indices of RAAS including PRR, renin, angiotensin II and aldosterone levels were examined by immunoblotting, qRT-PCR or ELISA. Further analyses of renal ENaC expression, sodium-water r...
Source: Am J Physiol Renal P... - October 31, 2018 Category: Urology & Nephrology Authors: Fu Z, Hu J, Zhou L, Chen Y, Deng M, Liu X, Su J, Lu A, Yang T Tags: Am J Physiol Renal Physiol Source Type: research

Global Polysome Analysis of Normal and Injured Podocytes.
Abstract Podocyte injury is a key event for progressive renal failure. We have previously established a mouse model of inducible podocyte injury (NEP25) that progressively develops glomerulosclerosis after immunotoxin injection. We performed polysome analysis of intact and injured podocytes utilizing the NEP25 and RiboTag transgenic mice, in which a hemagglutinin-tag is attached to ribosomal protein L22 selectively in podocytes. Podocyte-specific polysomes were successfully obtained by immunoprecipitation with an anti-hemagglutinin antibody from glomerular homogenate and analyzed using a microarray. Compared to gl...
Source: Am J Physiol Renal P... - October 31, 2018 Category: Urology & Nephrology Authors: Okabe M, Motojima M, Miyazaki Y, Pastan I, Yokoo T, Matsusaka T Tags: Am J Physiol Renal Physiol Source Type: research

Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury.
e JÁ Abstract The aim of this study is the identification of metabolomic biomarkers of sepsis and sepsis-induced acute kidney injury (AKI) in an experimental model. Pigs were anesthetized and monitored to measure mean arterial pressure (MAP), systemic blood flow (QT), mean pulmonary arterial pressure (MPAP), renal artery blood flow (QRA), renal cortical blood flow (QRC), and urine output (UO). Sepsis was induced at t=0 min by the administration of live Escherichia coli (n=6) or saline (n=8). At t=300 min, animals were sacrificed. Renal tissue, urine and serum samples were analyzed by Nuclear Magnetic Resona...
Source: Am J Physiol Renal P... - October 31, 2018 Category: Urology & Nephrology Authors: Izquierdo-Garcia JL, Nin N, Cardinal-Fernandez P, Rojas Y, de Paula M, Granados R, Martínez-Caro L, Ruiz-Cabello J, Lorente JÁ Tags: Am J Physiol Renal Physiol Source Type: research

Nitric oxide mediates anomalous tubuloglomerular feedback in rats fed high NaCl diet after subtotal nephrectomy.
Abstract Tubuloglomerular feedback (TGF) responses become anomalous in rats fed high NaCl diet after subtotal nephrectomy (STN) such that stimulating TGF causes single nephron GFR (SNGFR) to increase rather than decrease. Micropuncture experiments were performed to determine whether this anomaly results from heightened nitric oxide response to distal delivery, which is a known mechanism for resetting TGF, or from connecting tubule TGF (cTGF), which is a novel amiloride-inhibitable system for offsetting TGF responses. Micropuncture was done in Wistar Froemter rats fed high NaCl diet (HS) for 8-10 days after STN or ...
Source: Am J Physiol Renal P... - October 31, 2018 Category: Urology & Nephrology Authors: Thomson SC Tags: Am J Physiol Renal Physiol Source Type: research

Plasma Syndecan-1 in Hemodialysis Patients Associates with Survival and Lower Markers of Volume Status.
Abstract Syndecan-1, a transmembrane heparan sulfate proteoglycan, associates with renal and cardiovascular functioning. We earlier reported syndecan-1 to be involved in renal tubular regeneration. We now examined plasma values of syndecan-1 in a hemodialysis cohort and its association with volume, inflammatory and endothelial markers in addition to outcome. Predialysis syndecan-1 levels were two-fold higher in males compared to females (P=0.0003). Patients in the highest predialysis plasma syndecan-1 tertile had a significantly higher ultrafiltration rate (P=0.034) and lower plasma values of BNP (P=0.019), pro-AN...
Source: Am J Physiol Renal P... - October 31, 2018 Category: Urology & Nephrology Authors: Koch J, Idzerda NMA, Dam W, Assa S, Franssen CF, van den Born J Tags: Am J Physiol Renal Physiol Source Type: research