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Renal proximal tubule

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https://www.readbyqxmd.com/read/28932931/usefulness-of-zebrafish-larvae-to-evaluate-drug-induced-functional-and-morphological-renal-tubular-alterations
#1
Rita Gorgulho, Raquel Jacinto, Susana S Lopes, Sofia A Pereira, Erin M Tranfield, Gabriel G Martins, Emilio J Gualda, Rico J E Derks, Ana C Correia, Evelyne Steenvoorden, Petra Pintado, Oleg A Mayboroda, Emilia C Monteiro, Judit Morello
Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir...
September 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28931758/molecular-characterization-of-the-transition-from-acute-to-chronic-kidney-injury-following-ischemia-reperfusion
#2
Jing Liu, Sanjeev Kumar, Egor Dolzhenko, Gregory F Alvarado, Jinjin Guo, Can Lu, Yibu Chen, Meng Li, Mark C Dessing, Riana K Parvez, Pietro E Cippà, A Michaela Krautzberger, Gohar Saribekyan, Andrew D Smith, Andrew P McMahon
Though an acute kidney injury (AKI) episode is associated with an increased risk of chronic kidney disease (CKD), the mechanisms determining the transition from acute to irreversible chronic injury are not well understood. To extend our understanding of renal repair, and its limits, we performed a detailed molecular characterization of a murine ischemia/reperfusion injury (IRI) model for 12 months after injury. Together, the data comprising RNA-sequencing (RNA-seq) analysis at multiple time points, histological studies, and molecular and cellular characterization of targeted gene activity provide a comprehensive profile of injury, repair, and long-term maladaptive responses following IRI...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931009/ndfip-allows-nedd4-nedd4l-induced-aqp2-ubiquitination-and-degradation
#3
Christiane Trimpert, Daniel Wesche, Theun de Groot, Martha M Pimentel Rodriguez, Victoria Wong, Dennis T M van den Berg, Lydie Cheval, Carolina A Ariza, Alain Doucet, Igor Stagljar, Peter M T Deen
Regulation of our water homeostasis is fine-tuned by dynamic translocation of Aquaporin-2 (AQP2)-bearing vesicles to and from the plasma membrane of renal principal cells. Whereas binding of vasopressin to its type-2 receptor initiates a cAMP-protein kinase A cascade and AQP2 translocation to the apical membrane, this is counteracted by protein kinase C-activating hormones, resulting in ubiquitination-dependent internalization of AQP2. The proteins targeting AQP2 for ubiquitin-mediated degradation are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28929120/sulodexide-protects-renal-tubular-epithelial-cells-from-oxidative-stress-induced-injury-via-upregulating-klotho-expression-at-an-early-stage-of-diabetic-kidney-disease
#4
Yu Ning Liu, Jingwei Zhou, Tingting Li, Jing Wu, Shu Hua Xie, Hua-Feng Liu, Zhangsuo Liu, Tae Sun Park, Yaoxian Wang, Wei Jing Liu
The hypoalbuminuric effect of sulodexide (SDX) on diabetic kidney disease (DKD) was suggested by some clinical trials but was denied by the Collaborative Study Group. In this study, the diabetic rats were treated with SDX either from week 0 to 24 or from week 13 to 24. We found that 24-week treatment significantly decreased the urinary protein and HAVCR1 excretion, inhibited the interstitial expansion, and downregulated the renal cell apoptosis and interstitial fibrosis. Renoprotection was also associated with a reduction in renocortical/urinary oxidative activity and the normalization of renal klotho expression...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28926845/leptospirosis-renal-disease-emerging-culprit-of-chronic-kidney-disease-unknown-etiology
#5
Chih-Wei Yang
Leptospirosis is the most prevalent zoonosis affecting more than 1 million populations worldwide. Interestingly, leptospirosis endemic regions coincide with chronic kidney disease (CKD) hotspots largely due to flooding and agricultural overlaps. Acute leptospirosis induces multiple organ dysfunction including acute kidney injury and may predispose to CKD and end-stage renal disease, if not treated timely. Asymptomatic infection may carry the bacteria in the kidney and CKD progresses insidiously. Histologic finding of leptospirosis renal disease includes tubulointerstitial nephritis, interstitial fibrosis, and tubular atrophy...
September 20, 2017: Nephron
https://www.readbyqxmd.com/read/28920823/diagnosis-and-treatment-of-a-unilateral-renal-cystadenoma-in-an-african-lion-panthera-leo
#6
Ronan Eustace, Jacob Rubin, Kimberly A Thompson, Kyle Snowdon, James G Sikarskie, Colleen Monahan, Rebecca C Smedley
A renal tubular cystadenoma was diagnosed in a 14-yr-old male African lion (Panthera leo). During a routine health evaluation, a left renal mass was identified via physical examination, radiographs, and abdominal ultrasonography. The mass was 30 × 15 cm in size and had a thin capsule with central hypoechoic fluid, suggestive of a perirenal cyst. An exploratory celiotomy with partial nephrectomy was performed without complications. Histologically, the tumor was characterized by a thick fibrous capsule surrounding multiple, variable-sized cysts that markedly compressed the adjacent fibrotic and atrophied renal cortex...
September 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28919632/cd36-in-chronic-kidney-disease-novel-insights-and-therapeutic-opportunities
#7
REVIEW
Xiaochun Yang, Daryl M Okamura, Xifeng Lu, Yaxi Chen, John Moorhead, Zac Varghese, Xiong Z Ruan
CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates the binding and cellular uptake of long-chain fatty acids, oxidized lipids and phospholipids, advanced oxidation protein products, thrombospondin and advanced glycation end products, and has roles in lipid accumulation, inflammatory signalling, energy reprogramming, apoptosis and kidney fibrosis. Renal CD36 is mainly expressed in tubular epithelial cells, podocytes and mesangial cells, and is markedly upregulated in the setting of chronic kidney disease (CKD)...
September 18, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28904298/usefulness-of-urinary-biomarkers-for-nephrotoxicity-in-cynomolgus-monkeys-treated-with-gentamicin-cisplatin-and-puromycin-aminonucleoside
#8
Hiroshi Uchino, Junko Fujishima, Kaori Fukuoka, Teppei Iwakiri, Akira Kamikuri, Hidenori Maeda, Kazuhiro Nakama
The objective of this study was to investigate the availability of novel urinary biomarkers (BMs) such as total protein, albumin, β2-microglobulin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute nephrotoxicity in cynomolgus monkeys. Animals (total 9 males/3 groups) were administered gentamicin (GM) subcutaneously at 40 mg/kg for 7 days, cisplatin (CDDP) intravenously at 3 mg/kg once and puromycin aminonucleoside (PAN) intravenously at 20 mg/kg for 7 days...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904080/pressure-and-stretch-differentially-affect-proliferation-of-renal-proximal-tubular-cells
#9
Diane Felsen, Bianca J Diaz, Jie Chen, Juana Gonzalez, Marie Louise V Kristensen, Anja B Bohn, Brendan T Roth, Dix P Poppas, Rikke Nørregaard
Renal obstruction is frequently found in adults and children. Mechanical stimuli, including pressure and stretch in the obstructed kidney, contribute to damage; animal models of obstruction are characterized by increased cellular proliferation. We were interested in the direct effects of pressure and stretch on renal tubular cell proliferation. Human HKC-8 or rat NRK-52E proximal tubule cells were subjected to either pressure [0, 60 or 90 mmHg] or static stretch [0 or 20%] for 24 or 48 h. Cell proliferation was measured by cell counting, cell cycle analyzed by flow cytometry, and PCNA and Skp2 expression were determined by qPCR or western blot...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28889026/gnas-mutations-and-heterotopic-ossification
#10
Murat Bastepe
GNAS is a complex imprinted gene encoding the alpha-subunit of the stimulatory heterotrimeric G protein (Gsα). GNAS gives rise to additional gene products that exhibit exclusively maternal or paternal expression, such as XLαs, a large variant of Gsα that shows exclusively paternal expression and is partly identical to the latter. Gsα itself is expressed biallelically in most tissues, although the expression occurs predominantly from the maternal allele in a small set of tissues, such as renal proximal tubules...
September 6, 2017: Bone
https://www.readbyqxmd.com/read/28887310/histone-deacetylase-6-inhibition-reduces-cysts-by-decreasing-via-camp-and-ca2-in-knockout-mouse-models-of-polycystic-kidney-disease
#11
Murali K Yanda, Qiangni Liu, Valeriu Cebotaru, William B Guggino, Liudmila Cebotaru
Autosomal dominant polycystic kidney disease (ADPKD) is associated with progressive en-largement of multiple renal cysts, often leading to renal failure which cannot be prevented by an current treatment. Two proteins encoded by two genes are associated with ADPKD, PC1 (pkd1), primarily a signaling molecule, and PC2 (pkd2), a Ca2+ channel. Dysregulation of cAMP signaling is central to ADPKD but the molecular mechanism is unresolved. Here we studied the role of histone deacetylase 6 (HDAC6) in regulating cyst growth to test the possibility that in-hibiting HDAC6 might help manage ADPKD...
September 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28886014/downregulation-of-autophagy-is-associated-with-severe-ischemia-reperfusion-induced-acute-kidney-injury-in-overexpressing-c-reactive-protein-mice
#12
Ao Bian, Mingjun Shi, Brianna Flores, Nancy Gillings, Peng Li, Shirley Xiao Yan, Beth Levine, Changying Xing, Ming Chang Hu
C-reactive protein (CRP), was recently reported to be closely associated with poor renal function in patients with acute kidney injury (AKI), but whether CRP is pathogenic or a mere biomarker in AKI remains largely unclear. Impaired autophagy is known to exacerbate renal ischemia-reperfusion injury (IRI). We examined whether the pathogenic role of CRP in AKI is associated with reduction of autophagy. We mated transgenic rabbit CRP over-expressing mice (Tg-CRP) with two autophagy reporter mouse lines, Tg-GFP-LC3 mice (LC3) and Tg-RFP-GFP-LC3 mice (RG-LC3) respectively to generate Tg-CRP-GFP-LC3 mice (PLC3) and Tg-CRP-RFP-GFP-LC3 mice (PRG-LC3)...
2017: PloS One
https://www.readbyqxmd.com/read/28885375/tenofovir-alafenamide-nephrotoxicity-in-an-hiv-positive-patient-a-case-report
#13
Tessa K Novick, Michael J Choi, Avi Z Rosenberg, Blaithin A McMahon, Derek Fine, Mohamed G Atta
RATIONALE: Tenofovir alafenamide (TAF) is novel prodrug of Tenofovir, a nucleotide reverse transcriptase inhibitor. TAF is less nephrotoxic than its predecessor prodrug, tenofovir disoproxil fumarate (TDF). Tenofovir causes mitochondrial dysfunction and tubular injury when there is elevated accumulation in proximal tubule cells. TAF's unique pharmacokinetic profile enables provision of lower required doses for antiviral efficacy. Lower concentrations reach renal tubules minimizing intracellular accumulation and mitochondrial damage...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28882485/zinc-chloride-rapidly-stimulates-efflux-transporters-in-renal-proximal-tubules-of-killifish-fundulus-heteroclitus
#14
Alexander Zaremba, David S Miller, Gert Fricker
Multidrug resistance-related protein 2 (Mrp2) is an ATP-driven efflux pump at the luminal membrane in renal proximal tubules. It acts as detoxification mechanism by transporting xenobiotics and metabolic products into urine. The trace element zinc is essential for cellular growth, differentiation and survival. It modulates immune response and is used as dietary supplement. Here, we found that 0.1-10μM ZnCl2 rapidly stimulated transport of the Mrp2 probe substrate Texas Red (TR) in isolated killifish renal proximal tubules, which provide an established model system to measure efflux transporter activity by using fluorescent probe substrates, confocal microscopy and image analysis...
September 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28878224/mild-intracellular-acidification-by-dexamethasone-attenuates-mitochondrial-dysfunction-in-a-human-inflammatory-proximal-tubule-epithelial-cell-model
#15
T J J Schirris, J Jansen, M Mihajlovic, L P van den Heuvel, R Masereeuw, F G M Russel
Septic acute kidney injury (AKI) associates with poor survival rates and often requires renal replacement therapy. Glucocorticoids may pose renal protective effects in sepsis via stimulation of mitochondrial function. Therefore, we studied the mitochondrial effects of dexamethasone in an experimental inflammatory proximal tubule epithelial cell model. Treatment of human proximal tubule epithelial cells with lipopolysaccharide (LPS) closely resembles pathophysiological processes during endotoxaemia, and led to increased cytokine excretion rates and cellular reactive oxygen species levels, combined with a reduced mitochondrial membrane potential and respiratory capacity...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870626/immunoreactivity-of-urate-transporters-glut9-and-urat1-is-located-in-epithelial-cells-of-the-choroid-plexus-of-human-brains
#16
Naoya Uemura, Ryuta Murakami, Yoichi Chiba, Ken Yanase, Ryuji Fujihara, Masato Mashima, Koichi Matsumoto, Machi Kawauchi, Gotaro Shirakami, Masaki Ueno
It has been suggested that urate plays a protective role in neurons, while hyperuricemia is correlated with atherosclerosis and cardiovascular disease. However, whether there is a system that directly transports urate into the brain remains to be clarified. In this study, the localization of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), which are known to be representative reabsorptive urate transporters, was immunohistochemically examined in autopsied human brains. Immunoreactivity of GLUT9 was observed on the apical side of the cytoplasm of epithelial cells in the choroid plexus and in the cilia of ependymal cells of the human brain...
September 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28861952/use-of-sodium-glucose-cotransporter%C3%A2-2-inhibitors-in-older-patients-with-type%C3%A2-2-diabetes-mellitus
#17
Takahiro Kambara, Rei Shibata, Hiroyuki Osanai, Yoshihito Nakashima, Hiroshi Asano, Kazuyoshi Sakai, Toyoaki Murohara, Masayoshi Ajioka
AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. METHODS: A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. RESULTS: The mean age of the patients was 73...
September 1, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28860163/proximal-tubular-cannabinoid-1-receptor-regulates-obesity-induced-ckd
#18
Shiran Udi, Liad Hinden, Brian Earley, Adi Drori, Noa Reuveni, Rivka Hadar, Resat Cinar, Alina Nemirovski, Joseph Tam
Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB1R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis...
August 31, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28859984/epstein-barr-virus-encoded-latent-membrane-protein-1-induces-epithelial-to-mesenchymal-transition-by-inducing-v-set-ig-domain-containing-4-vsig4-expression-via-nf-kb-in-renal-tubular-epithelial-hk-2%C3%A2-cells
#19
Seung-Mi Kim, Se Won Oh, Sang Hyun Park, Dae Young Hur, Seung-Woo Hong, Sang Youb Han
The epithelial to mesenchymal transition (EMT), a hallmark of chronic kidney disease, is a key event in the conversion from tubular epithelial cells to myofibroblasts in renal fibrosis. Epstein-Barr virus (EBV) is a γ-herpes oncovirus associated with chronic kidney disease. However, the relationship between EBV and the EMT process in renal tubular epithelial cells is not well understood. Among EBV-latent genes, EBV-encoded latent membrane protein 1 (LMP1) induces EMT by regulating a variety of molecules in EBV-induced oncogenic transformation...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28859264/adefovir-induced-fanconi-syndrome-associated-with-osteomalacia
#20
Samel Park, Woo-Il Kim, Dai-Hyun Cho, Yeo-Joo Kim, Hong-Soo Kim, Ji-Hee Kim, Seung-Kuy Cha, Kyu-Sang Park, Ji-Hye Lee, Sang Mi Lee, Eun Young Lee
Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted...
September 1, 2017: Clinical and Molecular Hepatology
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