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American Journal of Physiology. Renal Physiology

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https://www.readbyqxmd.com/read/28179257/interplay-between-renal-endothelin-and-purinergic-signaling-systems
#1
Eman Y Gohar, Malgorzata Kasztan, David M Pollock
Alterations in extracellular fluid volume regulation and sodium balance may result in the development and maintenance of salt-dependent hypertension, a major risk factor for cardiovascular disease. Numerous pathways contribute to the regulation of sodium excretion and blood pressure, including endothelin and purinergic signaling. Increasing evidence suggests a link between purinergic receptor activation and endothelin production within the renal collecting duct as a means of promoting natriuresis. A better understanding of the relationship between these two systems, especially in regard to sodium homeostasis, will fill a significant knowledge gap and may provide novel antihypertensive treatment options...
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28179256/zebrafish-mesonephric-renin-cells-are-functionally-conserved-and-comprise-of-two-distinct-morphological-populations
#2
Sebastien A Rider, Helen C Christian, Linda J Mullins, Amelia R Howarth, Calum A MacRae, John J Mullins
Zebrafish provide an excellent model in which to assess the role of the renin-angiotensin system in renal development, injury and repair. In contrast to mammals, zebrafish kidney organogenesis terminates with the mesonephros. Despite this, the basic functional structure of the nephron is conserved across vertebrates. The relevance of teleosts for studies relating to the regulation of the renin-angiotensin system was established by assessing the phenotype and functional regulation of renin-expressing cells in zebrafish...
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28179255/calcium-channel-blockade-blunts-the-renal-effects-of-acute-nitric-oxide-synthase-inhibition-in-healthy-humans
#3
Alberto Montanari, Davide Lazzeroni, Giovanna Pelà, Antonio Crocamo, Yuliya Lytvyn, Luisa Musiari, Aderville Cabassi, David Z I Cherney
AIMS: To investigate whether blockade of calcium channels (CCs) or Angiotensin II Type 1 receptors 1 (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. METHODS: Fourteen sodium replete healthy volunteers underwent 90 minute infusions of 3.0 μg.kg.min-1 NG-nitro-L-arginine methylester (L-NAME), on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg Manidipine (MANI), or 50 mg losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR, inulin), renal blood flow (RBF, p-aminohippurate), urinary sodium (UNaV) and 8-isoprostane (U8-iso-PGF2αV - an oxidative stress marker) were measured...
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28179254/a-mathematical-model-of-the-rat-kidney-k-induced-natriuresis
#4
Alan M Weinstein
A model of the rat nephron (Am. J. Physiol. 308:F1098, 2015) has been extended with addition of medullary vasculature. Blood vessels contain solutes from the nephron model, plus additional species from the model of Atherton et al. (Am. J. Physiol. 247:F61, 1984), representing hemoglobin buffering. In contrast to prior models of the urine concentrating mechanism, reflection coefficients for DVR are near zero. Model unknowns are initial proximal tubule pressures and flows, connecting tubule pressure, and medullary interstitial pressures and concentrations...
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28179253/enac-activity-in-the-cortical-collecting-duct-of-hk%C3%AE-1-h-k-atpase-knockout-mice-is-uncoupled-from-na-intake
#5
Elena Mironova, I Jeanette Lynch, Jonathan M Berman, Michelle L Gumz, James D Stockand, Charles S Wingo
Modulation of the epithelial Na+ channel (ENaC) activity in the collecting duct (CD) is an important mechanism for normal Na+ homeostasis. ENaC activity is inversely related to dietary Na+ intake, in part, due to inhibitory paracrine purinergic regulation. Evidence suggests that H+,K+-ATPase activity in the CD also influences Na+ excretion. We hypothesized that renal H+,K+-ATPases affect Na+ reabsorption by the CD by modulating ENaC activity. ENaC activity in HKα1 H+,K+-ATPase knockout (HKα1-/-) mice was uncoupled from Na+ intake...
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28179252/aquaporin-2-membrane-targeting-still-a-conundrum
#6
Emma Tina Bisgaard Olesen, Robert A Fenton
The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis. In this brief review we assess the role of cyclic adenosine monophosphate (cAMP) and discuss the emerging concept that V2R-mediated AQP2 trafficking is cAMP-independent.
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28148533/inhibition-of-vascular-smooth-muscle-inward-rectifier-k-channels-restores-myogenic-tone-in-mouse-urinary-bladder-arterioles
#7
Nathan R Tykocki, Adrian D Bonev, Thomas Andrew Longden, Thomas J Heppner, Mark T Nelson
Prolonged decreases in urinary bladder blood flow are linked to overactive and underactive bladder pathologies. However, the mechanisms regulating bladder vascular reactivity are largely unknown. To investigate these mechanisms, we examined myogenic and vasoactive properties of mouse bladder feed arterioles (BFAs). Unlike similar-sized arterioles from other vascular beds, BFAs failed to constrict in response to increases in intraluminal pressure (5-80 mmHg). Consistent with this lack of myogenic tone, arteriolar smooth muscle cell membrane potential was hyperpolarized (-72...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28148532/meta-analysis-of-polycystic-kidney-disease-expression-profiles-defines-strong-involvement-of-injury-repair-processes
#8
Tareq B Malas, Chiara Formica, Wouter N Leonhard, Pooja Rao, Zoraide Granchi, Marco Roos, Dorien J M Peters, Peter A C 't Hoen
Polycystic Kidney Disease is a major cause of end-stage renal disease. The disease mechanisms are not well understood and the pathogenesis towards renal failure remains elusive. In this study, we present the first RNASeq analysis of a Pkd1-mutant mouse model in a combined meta-analysis with other published PKD expression profiles. We introduce the PKD signature, a set of 1515 genes that are commonly dysregulated in PKD studies. We show that the signature genes include many known and novel PKD-related genes and functions...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28148531/primary-proximal-tubule-hyperreabsorption-and-impaired-tubular-transport-counterregulation-determine-glomerular-hyperfiltration-in-diabetes-a-modeling-analysis
#9
Karen Melissa Hallow, Yeshitila Gebremichael, Gabriel Helmlinger, Volker Vallon
Glomerular hypertension and hyperfiltration in early diabetes is associated with development and progression of diabetic kidney disease. The tubular hypothesis of diabetic hyperfiltration proposes that it is initiated by a primary increase in sodium (Na) reabsorption in the proximal tubule (PT) and the resulting tubuloglomerular feedback (TGF) response and lowering of Bowman space pressure (PBow). Here we utilized a mathematical model of the human kidney to investigate over acute and chronic timescales the mechanisms responsible for the magnitude of the hyperfiltration response...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28148530/usp40-gene-knockdown-disrupts-glomerular-permeability-in-zebrafish
#10
Hisashi Takagi, Yukino Nishibori, Kan Katayama, Tomohisa Katada, Shohei Takahashi, Zentaro Kiuchi, Shin-Ichiro Takahashi, Hiroyasu Kamei, Hayato Kawakami, Yoshihiro Akimoto, Akihiko Kudo, Katsuhiko Asanuma, Hiromu Takematsu, Kunimasa Yan
Unbiased transcriptome profiling and functional genomics approaches have identified ubiquitin specific protease 40 (USP40) as a highly specific glomerular transcript. This gene product remains uncharacterized, and its biological function is completely unknown. Here, we showed that mouse and rat glomeruli exhibit specific expression of the USP40 protein, which migrated at 150 kDa and was exclusively localized in the podocyte cytoplasm of the adult kidney. Double-labeling immunofluorescence staining and confocal microscopy analysis of fetal and neonate kidney samples revealed that USP40 was also expressed in the vasculature, including in glomerular endothelial cells at the premature stage...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28122715/primary-cilia-regulate-the-osmotic-stress-response-of-renal-epithelial-cells-through-trpm3
#11
Brian J Siroky, Nancy K Kleene, Steven J Kleene, Charles D Varnell, Raven G Comer, Jialiu Liu, Lu Lu, Nolan W Pachciarz, John J Bissler, Bradley P Dixon
Primary cilia sense environmental conditions including osmolality, but whether cilia participate in osmotic response in renal epithelial cells is not known. Transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known. We hypothesized that primary cilia are required for maximal activation of the osmotic response of renal epithelial cells, and that ciliary TRPM3 and TRPV4 mediate that response...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28122714/sleeping-beauty-awakening-urothelium-from-its-slumber
#12
Zarine R Balsara, Xue Li
The bladder urothelium is essentially quiescent but regenerates readily upon injury. The process of urothelial regeneration harkens back to the process of urothelial development whereby urothelial stem/progenitor cells must proliferate and terminally differentiate to establish all three urothelial layers. How the urothelium regulates the level of proliferation and the timing of differentiation to ensure the precise degree of regeneration is of significant interest in the field. Without a carefully-orchestrated process, urothelial regeneration may be inadequate, thereby exposing the host to toxins or pathogens, or excessive, thereby setting the stage for tumor development...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28122713/diabetes-hypertension-and-chronic-kidney-disease-progression-role-of-dpp4
#13
Ravi Nistala, Virginia Savin
There is tremendous interest in the protein dipeptidyl peptidase 4 (DPP4) as a target in diabetes management and reduction of associated cardiovascular risk. The underlying reasons for this burgeoning interest are manifold. First, DPP4 inhibitor therapy in patients with Type 2 diabetes mellitus (T2DM) resulted in a reduction in proteinuria in the recently concluded "Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction 53" (SAVOR-TIMI 53) trial...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100505/-5r-5-hydroxytriptolide-ameliorates-lupus-nephritis-in-mrl-lpr-mice-by-preventing-infiltration-of-immune-cells
#14
Lu-Yao Zhang, Heng Li, Yan-Wei Wu, Lei Cheng, Yu-Xi Yan, Xiao-Qian Yang, Feng-Hua Zhu, Shi-Jun He, Wei Tang, Jian-Ping Zuo
(5R)-5-Hydroxytriptolide (LLDT-8), a triptolide derivative with low toxicity, was previously reported to have strong immunosuppressive effects both in vitro and in vivo, but it remains unknown whether LLDT-8 has a therapy effect on systemic lupus erythematosus. In this study, we aimed to investigate the therapeutic effects of LLDT-8 on lupus nephritis in MRL/lpr mice, a model of systemic lupus erythematosus. Compared with vehicle group, different clinical parameters were improved upon LLDT-8 treatment: prolonged life-span of mice, decreased proteinuria, downregulated blood urea nitrogen and serum creatinine, reduced glomerular IgG deposits, and ameliorated histopathology...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100504/a-new-microscope-for-the-kidney-mathematics
#15
Anita T Layton
N/A.
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100503/chronic-kidney-disease-promotes-chronic-inflammation-in-visceral-white-adipose-tissue
#16
Dong Mei Xiang, Xiu Zhen Song, Zhan Mei Zhou, Yang Liu, Xiao Yan Dai, Xiang Lan Huang, Fan Fan Hou, Qiu Gen Zhou
White adipose tissue plays an important role in the development of metabolic disturbance which is a common feature in patients with chronic kidney disease (CKD). The effect of CKD on white adipose tissue remains poorly appreciated. Here we evaluated the inflammatory potential of visceral white adipose tissue in a rat model of CKD. The results showed production of pro-inflammatory cytokines and infiltration of macrophage in the tissue were significantly increased in CKD rats than sham rats. Moreover, the primary adipocytes and stromal vascular fraction under the condition of CKD could trigger the inflammatory response in each other...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100502/rack1-regulates-angiotensin-ii-induced-contractions-of-shr-preglomerular-vascular-smooth-muscle-cells
#17
Xiao Zhu, Edwin K Jackson
The preglomerular microcirculation of spontaneously hypertensive rats (SHR) is hypersensitive to angiotensin II, and studies show that this is likely due to enhanced convergent signaling between G-protein subunits αq (Gαq; released by angiotensin II) and G-protein subunits βγ (Gβγ; released by Gi-coupled receptors) to active phospholipase C (PLC). Here we investigated the molecular basis for the enhanced convergent signaling between Gβγ and Gαq in SHR preglomerular vascular smooth muscle cells (PGVSMCs)...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100501/mdm2-mediates-fibroblast-activation-and-renal-tubulointerstitial-fibrosis-via-p53-independent-pathway
#18
Chen Ye, Hui Tang, Zheng Zhao, Chun-Tao Lei, Chao-Qun You, Jiao Zhang, Pan Gao, Fang-Fang He, Shan Chen, Yumei Wang, Chun Zhang, Hua Su
It is well-recognized that Murine Double Minute gene 2 (MDM2) plays a critical role in cell proliferation and inflammatory processes during tumorigenesis. Also it is reported that MDM2 is expressed in glomeruli and involved in podocyte injury. However, whether MDM2 is implicated in renal fibrosis remains unclear. Here we investigated the role of MDM2 in tubulointerstitial fibrosis (TIF). By immunohistochemical staining and western blotting we confirmed that MDM2 is up-regulated in tubulointerstitial compartment in TIF patients and Unilateral Urethral Obstruction (UUO) mice, which mainly originates from myofibroblasts...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100500/mononuclear-phagocyte-subpopulations-in-the-mouse-kidney
#19
James George, Jeremie M Lever, Anupam Agarwal
Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. While the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the current knowledge regarding classification of these cell in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100499/gremlin1-plays-a-key-role-in-kidney-development-and-renal-fibrosis
#20
Rachel H Church, Imran Ali, Mitchel Tate, Deborah Lavin, Arjun Krishnakumar, Helena M Kok, Roel Goldschmeding, Finian Martin, Derek Brazil
Grem1, an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and BMP signalling is critical to normal lung, kidney and limb development. Grem1 levels are increased in renal fibrotic conditions including acute kidney injury, diabetic nephropathy, chronic allograft nephropathy and immune glomerulonephritis. A small number of grem1-/- whole body knockout mice on a mixed genetic background (8 %) are viable, with a single, enlarged left kidney and grossly normal histology...
January 18, 2017: American Journal of Physiology. Renal Physiology
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