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American Journal of Physiology. Renal Physiology

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https://www.readbyqxmd.com/read/28077374/parallel-microarray-profiling-identifies-erbb4-as-a-determinant-of-cyst-growth-in-adpkd-and-a-prognostic-biomarker-for-disease-progression
#1
Andrew J Streets, Tajdida A Magayr, Linghong Huang, Laura Vergoz, Sandro Rossetti, Roslyn J Simms, Peter C Harris, Dorien J M Peters, Albert Cm Ong
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the fourth most common cause of end-stage renal disease. The disease course can be highly variable and treatment options are limited. To identify new therapeutic targets and prognostic biomarkers of disease, we conducted parallel discovery microarray profiling in normal and diseased human PKD1 cystic kidney cells. A total of 1515 genes and 5 miRNA were differentially expressed by more than two-fold in PKD1 cells. Functional enrichment analysis identified 30 dysregulated signalling pathways including the epidermal growth factor (EGF) receptor pathway...
January 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28077373/determination-of-renal-function-and-injury-using-near-infrared-fluorimetry-in-experimental-cardiorenal-syndrome
#2
Mizuko Ikeda, Rumie Wakasaki, Katie J Schenning, Thomas Swide, Jeong Heon Lee, M Bernie Miller, Hak Soo Choi, Sharon Anderson, Michael P Hutchens
Cardiorenal syndrome type 1 causes acute kidney injury but is poorly understood; animal models and diagnostic aids are lacking. Robust noninvasive measurements of glomerular filtration rate are required for injury models and clinical use. Several have been described but are untested in translational models and suffer from biologic interference. We developed a mouse model of cardiorenal syndrome and tested the novel near-infrared fluorophore, ZW800-1, to assess renal and cardiac function. We performed murine cardiac arrest and cardiopulmonary resuscitation followed by transthoracic echocardiography, 2- and 24h later...
January 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28077372/extracellular-microrna-signature-in-chronic-kidney-disease
#3
Jagdeesan Muralidharan, Ali Ramezani, Monica J Hubal, Susan Knoblach, Shashi Shrivastav, Sara Karandish, Richard Scott, Nirmal Maxwell, Savas Ozturk, Srinivasan Beddhu, Jeffrey B Kopp, Dominic S Raj
MicroRNAs (miRNAs) are noncoding RNAs that regulate post-transcriptional gene expression. In this study we characterized the circulating and urinary miRNA pattern associated with reduced glomerular filtration rate using Affymetrix GeneChip miR 4.0 in 28 patients with chronic kidney disease (CKD). Top miRNA discoveries from the human studies were validated in an Alb/TGF-β mouse model of CKD, and in rat renal proximal tubular cells (NRK52E) exposed to TGF-β1. Plasma and urinary levels of procollagen III N-terminal propeptide and collagen IV were elevated in patients with decreased estimated glomerular filtration rate (eGFR)...
January 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28077371/markers-of-endothelial-damage-in-patients-with-chronic-kidney-disease-on-hemodialysis
#4
Andrés Carmona, Maria Luisa Agüera, Carlos Luna Ruiz, Paula Buendia, Laura Calleros, Andrea Garcia-Jerez, Manuel Rodríguez-Puyol, Manuel Arias, Marta Arias-Guillen, Gabriel de Arriba, Jose Ballarin, Carmen Bernis, Elvira Fernandez, Sagrario Garcia-Rebollo, Javier Mancha, Gloria Del Peso, Estefania Perez, Esteban Poch, Jose M Portoles, Diego Rodriguez-Puyol, Rafael Sánchez-Villanueva, Felipe Sarro, Armando Torres, Alejandro Martin-Malo, Pedro Aljama, Rafael Ramirez, Julia Carracedo
Patients with stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (REDinREN, Madrid): 80 patients with diabetes mellitus (DM) and 80 patients without DM who were matched for clinical and demographic criteria...
January 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052876/pericyte-and-immune-cells-contribute-to-complement-activation-in-tubulointerstitial-fibrosis
#5
Sandhya Xavier, Ranjit K Sahu, Susan G Landes, Jing Yu, Ronald P Taylor, Srinivas Ayyadevara, Judit Megyesi, William B Stallcup, Jeremy S Duffield, Edimara S Reis, John D Lambris, Didier Portilla
We have examined the pathogenic role of increased complement expression and activation during kidney fibrosis. Here we show that PDGFRβ positive pericytes isolated from mice subjected to obstructive or folic acid injury secrete C1q. This was associated with increased production of proinflammatory cytokines, extracellular matrix components, collagens and increased Wnt3a-mediated activation of Wnt/β-catenin signaling, that are hallmarks of myofibroblast activation. Real-time PCR, immunoblots, immunohistochemistry and flow cytometry analysis performed in whole kidney tissue confirmed increased expression of C1q, C1r, C1s as well as complement activation measured as increased synthesis of C3 fragments predominantly in the interstitial compartment...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052875/liver-x-receptor-%C3%AE-lxr%C3%AE-increases-aqp2-protein-level-via-a-post-transcriptional-mechanism-in-renal-collecting-ducts
#6
Wen Su, Shi-Zheng Huang, Min Gao, Xiao-Mu Kong, Jan-Ake Gustafsson, Su-Juan Xu, Bing Wang, Feng Zheng, Li-Hong Chen, Nan-Ping Wang, You-Fei Guan, Xiao-Yan Zhang
Liver X Receptors (LXRs) including LXRα and LXRβ are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRβ but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRβ regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRβ-/- mice exhibited a reduced response to dDAVP stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052874/inhibition-of-hdac6-protects-against-rhabdomyolysis-induced-acute-kidney-injury
#7
Shi Yingfeng, Xu Liuqing, Tang Jinhua, Fang Lu, Ma Shuchen, Ma Xiaoyan, Nie Jing, Pi Xiaoling, Qiu Andong, Zhuang Shougang, Liu Na
Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the therapeutic effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction, expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules and increase of TUNEL positive tubular cells...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052873/path-of-translational-discovery-of-urological-complications-of-obesity-and-diabetes-ucod
#8
Firouz Daneshgari, Guiming Liu, Ann T Hanna-Mitchell
Diabetes Mellitus (DM) is a prevalent chronic disease. Type 1 diabetes mellitus (T1DM) is a metabolic disorder that is characterized by hyperglycemia in the context of absolute lack of insulin; whereas type 2 diabetes mellitus (T2DM) is due to insulin resistance-related relative insulin deficiency. Obesity is an established risk factor for T2DM. In comparison with T1DM, T2DM is more complex. The natural history of T2DM in most patients typically involves a course of obesity to impaired glucose tolerance, to insulin resistance and hyperglycemia...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052872/fgfr2-is-integral-for-bladder-mesenchyme-patterning-and-function
#9
Youko Ikeda, Irina Zabbarova, Caitlin M Schaefer, Daniel S Bushnell, William C de Groat, Anthony J Kanai, Carlton M Bates
BACKGROUND: While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown fibroblast growth factor receptor 2 (Fgfr2) is necessary for kidney and ureter mesenchymal development. OBJECTIVE: Out objective was to determine the role of Fgfr2 in bladder mesenchyme. METHODS: We used Tbx18cre mice to delete Fgfr2 in bladder mesenchyme (Fgfr2BM-/-)...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052871/myoglobin-facilitates-angiotensin-ii-induced-constriction-of-renal-afferent-arterioles
#10
Zhi Zhao Liu, Susanne Mathia, Tamara Margit Pahlitzsch, Inggrid Christine Wennysia, Pontus B Persson, En Yin Lai, Anica Högner, Min Ze Xu, Rudolf Schubert, Christian Rosenberger, Andreas Patzak
Vasoconstriction plays an important role in the development of acute kidney injury in rhabdomyolysis. We hypothesized that myoglobin enhances the angiotensin II (Ang II) response in afferent arterioles by increasing superoxide and reducing nitric oxide (NO) bioavailability. Afferent arterioles of C57Bl6 mice were isolated perfused and vasoreactivity was analyzed using video microscopy. NO bioavailability, superoxide concentration in the vessels wall, and changes in cytosolic calcium were measured using fluorescence techniques...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052870/phosphodiesterase-5-inhibition-ameliorates-angiotensin-ii-dependent-hypertension-and-renal-vascular-dysfunction
#11
Manuel Thieme, Sema Hayriye Sivritas, Evanthia Mergia, Sebastian Alexander Potthoff, Guang Yang, Lydia Hering, Katharina Grave, Henning Hoch, Lars Christian Rump, Johannes Stegbauer
Changes in renal hemodynamics have a major impact on blood pressure (BP). Angiotensin (Ang) II has been shown to induce vascular dysfunction by interacting with phosphodiesterases (PDE)1 and PDE5. The predominant PDE isoform responsible for renal vascular dysfunction in hypertension is unknown. Here, we measured effects of PDE5-(sildenafil) or PDE1-(vinpocetine) inhibition on renal blood flow (RBF), BP and renal vascular function in normotensive and hypertensive mice. During acute short-term Ang II infusion, sildenafil decreased BP and increased RBF in C57BL/6 (WT) mice...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28052869/nlrp3-inflammasome-activation-contributes-to-aldosterone-induced-podocyte-injury
#12
Mi Bai, Ying Chen, Min Zhao, Yue Zhang, John Cijiang He, Songming Huang, Zhanjun Jia, Aihua Zhang
Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NLRP3 inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1 and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by a mineralocorticoid receptor antagonist Eplerenone (EPL) or an antioxidant NAC...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28031172/prorenin-receptor-controls-renal-branching-morphogenesis-via-wnt-%C3%AE-catenin-signaling
#13
Renfang Song, Adam Janssen, Yuwen Li, Samir S El-Dahr, Ihor V Yosypiv
The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H+-ATPase. Renal branching morphogenesis, defined as growth and branching of the ureteric bud (UB), is essential for mammalian kidney development. Previously, we demonstrated that conditional ablation of the PRR in the UB in PRRUB-/- mice causes severe defects in UB branching, resulting in marked kidney hypoplasia at birth. Here, we investigated UB transcriptome using whole-genome-based analysis of gene expression in UB cells FACS-isolated from PRRUB-/- and control kidneys at birth (P0) to determine the primary role of the PRR in terminal differentiation and growth of UB-derived collecting ducts...
December 28, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28031171/whole-body-acid-base-modeling-revisited
#14
Troels Ring, Søren Nielsen
The textbook account of whole-body acid-base balance in terms of endogenous acid production, renal net acid excretion and gastrointestinal alkali absorption which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. In order to improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production was already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions...
December 28, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28031170/the-influence-of-sex-on-hyperfiltration-in-patients-with-uncomplicated-type-1-diabetes
#15
Marko Škrtić, Yuliya Lytvyn, Petter Bjornstad, Heather N Reich, James W Scholey, Paul M Yip, Etienne B Sochett, Bruce A Perkins, David Z I Cherney
The aim of this analysis was to examine sex-based differences in renal segmental resistances in healthy controls (HC) and patients with type 1 diabetes (T1D). We hypothesized that hyperfiltration - an early hemodynamic abnormality associated with diabetic nephropathy (DN) - would disproportionately affect women with T1D, thereby attenuating protection against the development of renal complications. Glomerular hemodynamic parameters were evaluated in HC (n=30) and in normotensive, normoalbuminuric patients with T1D and either baseline normofiltration (n=36, T1D-N, glomerular filtration rate [GFR] 90-134 ml/min/1...
December 28, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28031169/the-hypoxanthine-xanthine-oxidase-axis-is-not-involved-in-the-initial-phase-of-clinical-transplantation-related-ischemia-reperfusion-injury
#16
Leonie G M Wijermars, Jaap A Bakker, Dorottya K de Vries, Cornelis J F van Noorden, Jorgen Bierau, Sarantos Kostidis, Oleg A Mayboroda, Dimitrios Tsikas, Alexander F Schaapherder, Jan H N Lindeman
The hypoxanthine-xanthine oxidase (XO) axis is considered to be a key driver of transplantation related ischemia reperfusion (I/R) injury. Whereas interference with this axis effectively quenches I/R injury in preclinical models, there is limited efficacy of XO inhibitors in clinical trials. In this context, we considered clinical evaluation of a role for the hypoxanthine-XO axis in human I/R to be relevant. Patients undergoing renal allograft transplantation were included (n=40) and classified based on duration of ischemia (short; intermediate; prolonged)...
December 28, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28003191/calcineurin-inhibitor-cyclosporine-a-activates-renal-na-k-cl-cotransporters-via-local-and-systemic-mechanisms
#17
Katharina Ilse Blankenstein, Aljona Borschewski, Robert Labes, Alexander Paliege, Christin Boldt, James A McCormick, David H Ellison, Michael Bader, Sebastian Bachmann, Kerim Mutig
Calcineurin dephosphorylates NFAT transcription factors, thereby facilitating T-cell mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation, but may cause side effects including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA)...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28003190/the-effects-of-exogenous-desmopressin-on-a-model-of-heat-stress-nephropathy-in-mice
#18
Carlos A Roncal-Jimenez, Tamara Milagres, Ana Andres-Hernando, Masanari Kuwabara, Thomas Jensen, Zhilin Song, Petter Bjornstad, Gabriela E Garcia, Yuka Sato, Laura-Gabriela Sanchez-Lozada, Miguel A Lanaspa, Richard J Johnson
BACKGROUND: Recurrent heat stress and dehydration have recently been shown experimentally to cause chronic kidney disease (CKD). One potential mediator may be vasopressin, acting via the type 2 vasopressin receptor (V2 receptor). We tested the hypothesis that desmopressin accelerates CKD in mice subjected to heat stress and recurrent dehydration. METHODS: Recurrent exposure to heat with limited water availability was performed in male mice over a 5 week period, with one group receiving desmopressin twice daily and the other group received vehicle...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28003189/involvement-of-enac-in-the-development-of-salt-sensitive-hypertension
#19
Tengis S Pavlov, Alexander Staruschenko
Salt-sensitive hypertension is associated with renal and vascular dysfunctions which lead to impaired fluid excretion, increased cardiac output and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron which plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28003188/insulin-like-growth-factor-binding-protein-7-and-tissue-inhibitor-of-metalloproteinases-2-differential-expression-and-secretion-in-human-kidney-tubule-cells
#20
David R Emlet, Nuria Pastor-Soler, Allison Marciszyn, Xiaoyan Wen, Hernando Gomez, William H Humphries, Seth Morrisroe, Jacob K Volpe, John A Kellum
We have characterized the expression and secretion of the acute kidney injury biomarkers Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) and Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin...
December 21, 2016: American Journal of Physiology. Renal Physiology
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