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https://www.readbyqxmd.com/read/28819999/high-glucose-induces-hgf-independent-activation-of-met-receptor-in-human-renal-tubular-epithelium
#1
Lucia Mesarosova, Peter Ochodnicky, Jaklien C Leemans, Sandrine Florquin, Peter Krenek, Jan Klimas
CONTEXT: The role of hepatocyte growth factor (HGF) in diabetic kidney damage remains controversial. OBJECTIVE: To test the hypothesis that high glucose levels activate pathways related to HGF and its receptor Met and that this could participate in glucose-induced renal cell damage. MATERIALS AND METHODS: HK2 cells, a human proximal tubule epithelial cell line, were stimulated with high glucose for 48 hours. Levels of pMet/Met, pEGFR/EGFR, pSTAT3/STAT3, pAkt/Akt and pERK1/2/ERK1/2 were studied by immunoblotting...
August 18, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28817830/microrna-200a-inhibits-transforming-growth-factor-%C3%AE-1-induced-proximal-tubular-epithelial-mesenchymal-transition-by-targeting-%C3%AE-catenin
#2
Yi Gong, Zhexue Qin, Baoshang Zhou, Hua Chen, Zhengmin Shi, Jing Zhang
BACKGROUND: The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin...
August 18, 2017: Nephron
https://www.readbyqxmd.com/read/28815213/identification-of-rab18-as-an-essential-host-factor-for-bk-polyomavirus-infection-using-a-whole-genome-rna-interference-screen
#3
Linbo Zhao, Michael J Imperiale
BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. To establish a successful infection in host cells, BKPyV must travel in retrograde transport vesicles to reach the nucleus. To make this happen, BKPyV requires the cooperation of host cell proteins...
July 2017: MSphere
https://www.readbyqxmd.com/read/28813167/lipophagy-maintains-energy-homeostasis-in-the-kidney-proximal-tubule-during-prolonged-starvation
#4
Satoshi Minami, Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Tomonori Kimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Yoshitaka Isaka
Macroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use. The involvement of autophagy in lipid metabolism in the kidney remains largely unknown. Here, we investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation using PTC-specific Atg5-deficient (atg5-TSKO) mice and an in vitro serum starvation model...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28813008/dietary-fructose-enhances-the-ability-of-low-concentrations-of-angiotensin-ii-to-stimulate-proximal-tubule-na%C3%A2-%C2%BA-reabsorption
#5
Agustin Gonzalez-Vicente, Pablo D Cabral, Nancy J Hong, Jessica Asirwatham, Nianxin Yang, Jessica M Berthiaume, Fernando P Dominici, Jeffrey L Garvin
Fructose-enriched diets cause salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the water and salt filtered through the glomerulus. Angiotensin II (Ang II) regulates this process. Normally, dietary salt reduces Ang II allowing the kidney to excrete more salt, thereby preventing hypertension. We hypothesized that fructose-enriched diets enhance the ability of low concentrations of Ang II to stimulate PT transport. We measured the effects of a low concentration of Ang II (10(-12) mol/L) on transport-related oxygen consumption (QO₂), and Na/K-ATPase and Na/H-exchange (NHE) activities and expression in PTs from rats consuming tap water (Control) or 20% fructose (FRUC)...
August 16, 2017: Nutrients
https://www.readbyqxmd.com/read/28812381/retrospective-review-of-sglt2-inhibitor-exposures-reported-to-13-poison-centers
#6
Scott E Schaeffer, Carol DesLauriers, Henry A Spiller, Alfred Aleguas, Salvador Baeza, Mark L Ryan
BACKGROUND: SGLT2 inhibitors are a new class of oral antidiabetics prescribed in the United States since 2013. They act by inhibiting reabsorption of glucose in the proximal convoluted tubule of the kidney, allowing excess glucose to be excreted. Little has been reported regarding effects of non-therapeutic exposure to this class of medication. METHODS: Retrospective records from 13 poison centers were examined for human exposures to SGLT2 inhibitors between 1st January 2013 and 31st December 2016...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28807932/reducing-inflammatory-cytokine-production-from-renal-collecting-duct-cells-by-inhibiting-gata2-ameliorates-acute-kidney-injury
#7
Lei Yu, Takashi Moriguchi, Hiroshi Kaneko, Makiko Hayashi, Atsushi Hasegawa, Masahiro Nezu, Hideyuki Saya, Masayuki Yamamoto, Ritsuko Shimizu
Acute kidney injury (AKI) is a leading cause of chronic kidney disease. Proximal tubules are considered to be the primary origin of pathogenic inflammatory cytokines in AKI. However, it remains unclear whether other cell types, including collecting duct (CD) cells, participate in inflammatory processes. The transcription factor GATA2 is specifically expressed in CD cells and maintains their cellular identity. To explore the pathophysiological function of GATA2 in AKI, we generated renal tubular cell-specific Gata2 deletion (G2CKO) mice and examined their susceptibility to ischemia-reperfusion injury (IRI)...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28807910/24-hour-pharmacokinetic-relationships-for-vancomycin-and-novel-urinary-biomarkers-of-acute-kidney-injury
#8
J Nicholas O'Donnell, Nathaniel J Rhodes, Thomas P Lodise, Walter C Prozialeck, Cristina M Miglis, Medha Joshi, Natarajan Venkatesan, Gwendolyn Pais, Cameron Cluff, Peter C Lamar, Seema Briyal, John Z Day, Anil Gulati, Marc H Scheetz
Introduction: Vancomycin has been associated with acute kidney injury in preclinical and clinical settings, however the precise exposure profiles associated with vancomycin induced acute kidney injury has not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kidney injury using sensitive urinary biomarkers.Methods: Male Sprague-Dawley rats received clinical grade vancomycin or normal saline as an intraperitoneal injection. Total daily doses between 0 and 400 mg/kg/day were administered as single or 2 divided doses over a 24-hour period...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28806702/hmgb1-redox-during-sepsis
#9
Wasan Abdulmahdi, Devika Patel, May M Rabadi, Tala Azar, Edson Jules, Mark Lipphardt, Rameen Hashemiyoon, Brian B Ratliff
During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis...
August 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28805677/endocytosis-of-albumin-induces-matrix-metalloproteinase-9-by-activating-the-erk-signaling-pathway-in-renal-tubule-epithelial-cells
#10
Xiaoming Chen, Alyssa Cobbs, Jasmine George, Ashmeer Chima, Fidele Tuyishime, Xueying Zhao
Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose. We also used specific inhibitors to determine if internalization of albumin and/or extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were required for MMP-9 secretion...
August 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28801787/reduction-of-68-ga-psma-renal-uptake-with-mannitol-infusion-preliminary-results
#11
Federica Matteucci, Emilio Mezzenga, Paola Caroli, Valentina Di Iorio, Anna Sarnelli, Monica Celli, Lorenzo Fantini, Andrea Moretti, Riccardo Galassi, Ugo De Giorgi, Giovanni Paganelli
PURPOSE: Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with (68)Ga or (177)Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of (68)Ga-PSMA...
August 11, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28794148/tubulointerstitial-nephritis-with-igm-positive-plasma-cells
#12
Naoki Takahashi, Takako Saeki, Atsushi Komatsuda, Chishio Munemura, Takeaki Fukui, Naofumi Imai, Noriyuki Homma, Tsuguru Hatta, Ken-Ichi Samejima, Takashi Fujimoto, Hiroki Omori, Yumi Ito, Yudai Nishikawa, Mamiko Kobayashi, Yukie Morikawa, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Kenji Kasuno, Hideki Kimura, Tomoyuki Nemoto, Yasunari Nakamoto, Kiyonao Sada, Manabu Sugai, Hironobu Naiki, Haruyoshi Yoshida, Ichiei Narita, Yoshihiko Saito, Masayuki Iwano
Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected...
August 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28793269/cell-type-specific-gene-programs-of-the-normal-human-nephron-define-kidney-cancer-subtypes
#13
David Lindgren, Pontus Eriksson, Krzysztof Krawczyk, Helén Nilsson, Jennifer Hansson, Srinivas Veerla, Jonas Sjölund, Mattias Höglund, Martin E Johansson, Håkan Axelson
Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28777442/microphysiological-systems-to-assess-nonclinical-toxicity
#14
Kirk P Van Ness, Shih-Yu Chang, Elijah J Weber, Danielle Zumpano, David L Eaton, Edward J Kelly
The liver and the kidney are key toxicity target organs during drug development campaigns, as they typically carry the burden of drug transport and metabolism. Primary hepatocytes and proximal tubule epithelial cells grown in traditional in vitro 2-D culture systems do not maintain transporter and metabolic functions, thus limiting their utility for nonclinical toxicology investigations. We have developed a renal and hepatic microphysiological system (MPS) platform that uses a commercially available MPS device as the core cell culture platform for our methodologies...
August 4, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28774999/sexual-dimorphic-pattern-of-renal-transporters-and-electrolyte-homeostasis
#15
Luciana C Veiras, Adriana C C Girardi, Joshua Curry, Lei Pei, Donna L Ralph, An Tran, Regiane C Castelo-Branco, Nuria Pastor-Soler, Cristina T Arranz, Alan S L Yu, Alicia A McDonough
Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did...
August 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28771454/%C3%AE-ketoglutarate-drives-electroneutral-nacl-reabsorption-in-intercalated-cells-by-activating-a-g-protein-coupled-receptor-oxgr1
#16
Paul R Grimm, Paul A Welling
PURPOSE OF REVIEW: This review describes the recent discoveries about a powerful electroneutral NaCl reabsorption mechanism in intercalated cells, and its regulation by an intrarenal metabolite paracrine, α-ketoglutartate, and the G-protein coupled receptor, Oxgr1. RECENT FINDINGS: The distal nephron fine-tunes sodium, chloride, potassium, hydrogen, bicarbonate and water transport to maintain electrolyte homeostasis and blood pressure. Intercalated cells have been traditionally viewed as the professional regulators of acid-base balance, but recent studies reveal that a specific population of intercalated cells, identified by the pendrin-transporter, have a surprising role in the regulation of salt balance...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28769101/allostimulatory-capacity-of-conditionally-immortalized-proximal-tubule-cell-lines-for-bioartificial-kidney-application
#17
Milos Mihajlovic, Lambertus P van den Heuvel, Joost G Hoenderop, Jitske Jansen, Martijn J Wilmer, Annemarie J F Westheim, Wil A Allebes, Dimitrios Stamatialis, Luuk B Hilbrands, Rosalinde Masereeuw
Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily available conditionally immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were characterized for the expression and secretion of relevant molecules involved in alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40, CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6, IL-8 and TNF-α)...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28769002/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-luseogliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-japanese-patients-with-type-2-diabetes-mellitus
#18
Yoshishige Samukawa, Masaru Mutoh, Shi Chen, Nobuo Mizui
Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by promoting urinary glucose excretion (UGE). A clinical pharmacology study conducted in Japanese patients with T2DM confirmed dose-dependency of UGE with once-daily administration of luseogliflozin; however, the reason for sustained UGE after plasma luseogliflozin decreased was unclear. To elucidate the effect of inhibition rate constants, Kon and Koff, and to explain the sustained UGE, a pharmacokinetic-pharmacodynamic (PK-PD) model was built based on the mechanisms of glucose filtration in the glomerulus and reabsorption in the renal proximal tubule of kidney as well as the kinetics of competitive inhibition of SGLT1/2 and inhibition rate constants of SGLT2, by using UGE and plasma glucose levels and luseogliflozin concentrations...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28768665/dopamine-reduces-cell-surface-na-h-exchanger-3-nhe3-protein-by-decreasing-nhe3-exocytosis-and-cell-membrane-recycling
#19
Ming Chang Hu, Ion Alexandru Bobulescu, Henry Quiñones, Serge M Gisler, Orson W Moe
The intrarenal autocrine-paracrine dopamine (DA) system mediates a significant fraction of the natriuresis in response to a salt load. DA inhibits a number of Na+ transporters to effect sodium excretion, including the proximal tubule Na+/H+ exchanger-3 (NHE3). DA represent a single hormone that regulates NHE3 at multiple levels including translation, degradation, endocytosis, and protein phosphorylation. Since cell surface NHE3 protein is determined by the balance between exocytotic insertion and endocytotic retrieval, we examined whether DA acutely affects the rate of NHE3 exocytosis in a cell culture model...
August 2, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28767797/evaluation-of-sepsis-treatment-with-enteral-glutamine-in-rats
#20
Isadora Moscardini Fabiani, Sérgio Luiz Rocha
Objective: to analyze the influence of glutamine on morphological and histological changes observed in the ileum, lung, kidney and liver of Wistar rats subjected to sepsis. Methods: we induced sepsis by cecal ligature and puncture. We divided the animals in two groups: group A, control, with five animals, and group B, experience, with ten animals that received enteral glutamine two days before sepsis induction. We used histological analysis to rank the injury according to a score dependent on the injury severity and the affected organ...
May 2017: Revista do Colégio Brasileiro de Cirurgiões
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