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Proximal tubule

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https://www.readbyqxmd.com/read/29029121/clinical-heterogeneity-and-phenotypic-expansion-of-napi-iia-associated-disease
#1
Korcan Demir, Melek Yildiz, Hilla Bahat, Michael Goldman, Nisreen Hassan, Shay Tzur, Ayala Ofir, Daniella Magen
Context: NaPi-IIa, encoded by SLC34A1 is a key phosphate transporter in the mammalian proximal tubule, and plays a cardinal role in renal phosphate handling. NaPi-IIa impairment has been linked to various overlapping clinical syndromes, including hypophosphatemic nephrolithiasis with osteoporosis, renal Fanconi's syndrome with chronic kidney disease, and most recently, with idiopathic infantile hypercalcemia and nephrocalcinosis. Objectives: We studied the molecular basis of idiopathic infantile hypercalcemia with partial proximal tubulopathy in two apparently unrelated patients of Israeli and Turkish descent...
September 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29021995/tumor-induced-osteomalacia
#2
Pablo Florenzano, Rachel I Gafni, Michael T Collins
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23) that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/29021386/suppression-of-microrna-activity-in-kidney-collecting-ducts-induces-partial-loss-of-epithelial-phenotype-and-renal-fibrosis
#3
Sachin Hajarnis, Matanel Yheskel, Darren Williams, Thomas Brefort, Bob Glaudemans, Huguette Debaix, Michel Baum, Olivier Devuyst, Vishal Patel
microRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. The physiologic function of these noncoding RNAs in postnatal renal tubules still remains unclear. Surprisingly, they appear to be dispensable for mammalian proximal tubule (PT) function. Here, we examined the effects of miRNA suppression in collecting ducts (CDs). To conclusively evaluate the role of miRNAs, we generated three mouse models with CD-specific inactivation of key miRNA pathway genes Dicer, Dgcr8, and the entire Argonaute gene family (Ago1, 2, 3, and 4)...
October 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29021225/atp-induces-pad4-in-renal-proximal-tubule-cells-via-p2x7-receptor-activation-to-exacerbate-ischemic-aki
#4
May M Rabadi, Mihwa Kim, Hongmei Li, Sang Jun Han, Yewoon Choi, Vivette Denise D'Agati, H Thomas Lee
We previously demonstrated that renal tubular peptidylarginine deiminase-4 (PAD4) is induced after ischemia reperfusion (IR) injury and this induction of PAD4 exacerbates ischemic acute kidney injury (AKI) by promoting renal tubular inflammation and neutrophil infiltration. However, the mechanisms of renal tubular PAD4 induction after IR remain unknown. Here, we tested the hypothesis that ATP, a pro-inflammatory danger associated molecular pattern (DAMP) ligand released from necrotic cells after IR injury, induces renal tubular PAD4 and exacerbates ischemic AKI via P2 purinergic receptor activation...
October 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29020011/a-microfluidic-renal-proximal-tubule-with-active-reabsorptive-function
#5
Else M Vedula, José Luis Alonso, M Amin Arnaout, Joseph L Charest
In the kidney, the renal proximal tubule (PT) reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier...
2017: PloS One
https://www.readbyqxmd.com/read/29018138/endotoxin-preconditioning-reprograms-s1-tubules-and-macrophages-to-protect-the-kidney
#6
Takashi Hato, Amy Zollman, Zoya Plotkin, Tarek M El-Achkar, Bernhard F Maier, S Louise Pay, Shataakshi Dube, Pablo Cabral, Momoko Yoshimoto, Jeanette McClintick, Pierre C Dagher
Preconditioning with a low dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response generated by preconditioning remains unknown. Here, using the kidney as a model organ, we investigated cell type-specific responses to preconditioning. Compared with preadministration of vehicle, endotoxin preconditioning in the cecal ligation and puncture mouse model of sepsis led to significantly enhanced survival and reduced bacterial load in several organs...
October 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28994737/anti-inflammatory-pyranochalcone-derivative-attenuates-lps-induced-acute-kidney-injury-via-inhibiting-tlr4-nf-%C3%AE%C2%BAb-pathway
#7
Min Shi, Xiaoxi Zeng, Fan Guo, Rongshuang Huang, Yanhuan Feng, Liang Ma, Li Zhou, Ping Fu
Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of 5b against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28993569/immunolocalization-of-%C3%AE-catenin-e-cadherin-and-n-cadherin-in-neonate-and-adult-rat-kidney
#8
Naomi Terada, Mohammad Rabiul Karim, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
β-catenin, E-cadherin and N-cadherin are adhesion molecules that play important roles in organogenesis, tissue homeostasis, renal epithelial integrity and polarity. The present study demonstrated their immunolocalization in adult and neonate rat kidney. Membranous or cytoplasmic expression of β-catenin, E-cadherin and N-cadherin were seen in adult and developing renal tubular epithelial cells. Particularly, in adult kidney, E-cadherin and β-catenin were intensively expressed in distal renal tubules, whereas N-cadherin was expressed in proximal renal tubules...
October 6, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28993506/kidney-proximal-tubule-lipoapoptosis-is-regulated-by-fatty-acid-transporter-2-fatp2
#9
Shenaz Khan, Pablo D Cabral, William P Schilling, Zachary W Schmidt, Asif N Uddin, Amelia Gingras, Sethu M Madhavan, Jeffrey L Garvin, Jeffrey R Schelling
Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated uptake of fluorescently labeled NEFA in cultured proximal tubule cells and microperfused rat proximal tubules, with greater uptake from the apical surface than from the basolateral surface...
October 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28990525/a-human-proximal-tubular-epithelial-cell-model-to-explore-a-knowledge-gap-on-neonatal-drug-disposition
#10
Ahmed Reda, Anke Raaijmakers, Saskia van Dorst, Charlotte G G M Pauwels, Karel Allegaert, Mohamed A Elmonem, Rosalinde Masereeuw, Lambertus van den Heuvel, Elena Levtchenko, Fanny Oliveira Arcolino
BACKGROUND: Finding the right drug-dosage for neonates is still a challenge. Until now, neonatal doses are extrapolated from adults and children doses. However, there are differences between neonatal and adult kidney physiology that should be considered, especially when it comes to drug metabolism and/or transport. Studying renal drug disposition in neonates is limited by the lack of reliable human cell models. OBJECTIVE: To illustrate the feasibility of developing an in vitro model for neonatal proximal tubule epithelial cells (nPTECs) to study renal drug disposition at this age...
October 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28988709/identification-and-characterization-of-a-potent-and-selective-inhibitor-of-human-urate-transporter-1
#11
Ting Wu, Jiasheng Chen, Shuai Dong, Haixin Li, Ying Cao, Yuanxin Tian, Weimin Fu, Pingzheng Zhou, Baomin Xi, Jianxin Pang
BACKGROUND: Selective inhibitors of human urate transporter 1 (hURAT1) are considered to be effective treatment for hyperuricemia and gout, which can reduce the reabsorption of more than 90% of uric acid in the proximal tubule of the kidney. We aimed to design and synthesize a more potent hURAT1 based on the structure of Lesinurad (LU), which was reported to lower uric acid levels with IC50 value of hURAT1 (about 60μM). METHODS: A cell model was conducted and characterized via Real-time qRCR and Western blot...
May 6, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28988287/kinetic-measurements-of-di-and-tripeptide-and-peptidomimetic-drug-transport-in-different-kidney-regions-using-the-fluorescent-membrane-potential-sensitive-dye-dis-c3-3
#12
Othman A Alghamdi, Nicola King, Graham L Jones, Pierre D J Moens
Tri- and dipeptides are transported in the kidney by PEPT1 and PEPT2 isoforms. The aim of this study was to investigate differences in transport kinetics between renal brush border (BBMV) and outer medulla (OMMV) membrane vesicles (where PEPT1 and PEPT2 are sequentially available) for a range of di- and tripeptides and peptidomimetic drugs. This was accomplished through the use of the potential-sensitive fluorescent dye 3,3'-dipropylthiacarbocyanine iodide [DiS-C3-(3)]. BBMV and OMMV were prepared from the rat kidney using standard techniques...
October 7, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28986476/colistin-is-substrate-of-the-carnitine-organic-cation-transporter-2-octn2-slc22a5
#13
Michele Visentin, Zhibo Gai, Angelo Torozi, Christian Hiller, Gerd A Kullak-Ublick
Colistin is a polycation antibiotic used for the treatment of multidrug-resistance (MDR) gram-negative infections; nevertheless, its use is often limited by the high incidence of renal damage. The mechanism underlying colistin-induced nephrotoxicity is not known, but perhaps related to its accumulation in the renal cortex upon extensive reabsorption from the nascent urine. Because little is known about the membrane transport of colistin, the purpose of the present study was to characterize better the transport system involved in colistin renal handling by using HEK293 cells stably transfected with the main organic cation transporters expressed at the apical membrane of the proximal tubule...
October 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28979691/fascin-1-is-released-from-proximal-tubular-cells-in-response-to-calcineurin-inhibitors-cnis-and-correlates-with-isometric-vacuolization-in-kidney-transplanted-patients
#14
Conxita Jacobs-Cachá, Irina B Torres, Joan López-Hellín, Carme Cantarell, María A Azancot, Antonio Román, Francesc Moreso, Daniel Serón, Anna Meseguer, Eduard Sarró
Immunosuppression based on calcineurin inhibitors (CNIs) has greatly improved organ transplantation, although subsequent nephrotoxicity significantly hinders treatment success. There are no currently available specific soluble biomarkers for CNI-induced nephrotoxicity and diagnosis relies on renal biopsy, which is costly, invasive and may cause complications. Accordingly, identification of non-invasive biomarkers distinguishing CNI-induced kidney tubular damage from that of other etiologies would greatly improve diagnosis and enable more precise dosage adjustment...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28978534/nmr-spectroscopy-and-electron-microscopy-identification-of-metabolic-and-ultrastructural-changes-to-the-kidney-following-ischemia-reperfusion-injury
#15
Tafadzwa Chihanga, Qing Ma, Jenna D Nicholson, Hannah N Ruby, Richard E Edelmann, Prasad Devarajan, Michael A Kennedy
Cellular, molecular, and ultrastructural nephron changes associated with ischemia reperfusion injury-induced acute kidney injury (IRI-AKI) are not completely understood. Here, a multidisciplinary study was used to identify nephron changes in a mouse model of IRI-AKI. Histological analyses indicated distended Bowman's glomerular spaces and proximal and distal tubules. Increased filtrate volume in nephrons was caused by reduced water reabsorption by severely damaged proximal tubule brush borders and blocked flow of filtrate into collecting tubules by mucoprotein casts in distal tubules...
October 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28977780/urinary-mirnas-as-biomarkers-for-noninvasive-evaluation-of-radiation-induced-renal-tubular-injury
#16
Sagar Bhayana, Feifei Song, Jidhin Jacob, Paolo Fadda, Nicholas C Denko, Meng Xu-Welliver, Arnab Chakravarti, Naduparambil K Jacob
Radiation nephropathy is one of the common late effects in cancer survivors who received radiotherapy as well as in victims of radiation accidents. The clinical manifestations of radiation nephropathy occur months after exposure. To date, there are no known early biomarkers to predict the future development of radiation nephropathy. This study focuses on the development of urinary biomarkers providing readout of acute responses in renal tubular epithelial cells. An amplification-free hybridization-based nCounter assay was used to detect changes in mouse urinary miRNAs after irradiation...
October 4, 2017: Radiation Research
https://www.readbyqxmd.com/read/28963126/egf-regulation-of-proximal-tubule-cell-proliferation-and-vegf-a-secretion
#17
Diana Zepeda-Orozco, Hsiang M Wen, Bradley A Hamilton, Nandita S Raikwar, Christie P Thomas
Proximal tubule cell (PTC) proliferation is critical for tubular regeneration and recovery from acute kidney injury. Epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF-A) are important for the maintenance of tubulointerstitial integrity and can stimulate PTC proliferation. We utilized HK-2 cells, an immortalized human PTC line, to characterize the EGF-dependent regulation of VEGF-A secretion and proliferation in PTCs. We demonstrate that EGF stimulates VEGF-A secretion via the EGF receptor (EGFR) and stimulates cell proliferation via activation of the VEGF receptor, VEGFR-2...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28959658/comparison-of-diglycolic-acid-exposure-to-human-proximal-tubule-cells-in-vitro-and-rat-kidneys-in-vivo
#18
Miriam E Mossoba, Sanah Vohra, Howard Toomer, Shelia Pugh-Bishop, Zachary Keltner, Vanessa Topping, Thomas Black, Nicholas Olejnik, Ana Depina, Kathleen Belgrave, Jessica Sprando, Joyce Njorge, Thomas J Flynn, Paddy L Wiesenfeld, Robert L Sprando
Diglycolic acid (DGA) is present in trace amounts in our food supply and is classified as an indirect food additive linked with the primary GRAS food additive carboxymethyl cellulose (CMC). Carboxymethyl starches are used as a filler/binder excipient in dietary supplement tablets and a thickening ingredient in many other processed foods. We sought to utilize the human proximal tubule HK-2 cell line as an in vitro cellular model system to evaluate its acute nephrotoxicity of DGA. We found that DGA was indeed toxic to HK-2 cells in all in vitro assays in our study, including a highly sensitive Luminex assay that measures levels of an in vitro biomarker of kidney-specific toxicity, Kidney Injury Molecule 1 (KIM-1)...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28959634/safety-assessment-of-freeze-dried-powdered-cassiae-semen-evaluation-of-chronic-toxicity-26-week-in-sprague-dawley-rats
#19
Yanyu Pei, Ruoyao Wei, Jingjiang Sun, Hong Gao
There is a lack of safety assessment data regarding the long-term consumption of Cassiae Semen (Leguminosae, the seeds of Cassia obtusifolia L. and Cassia tora L.). Thus, we evaluated the toxicity of freeze-dried powdered Cassiae Semen in male and female Sprague-Dawley rats. Rats were intragastrically administered freeze-dried powdered Cassiae Semen at a dose of 0.5, 2.2, or 10.0 g/kg body weight/day for 26 weeks; several variables were assessed after 13 and 26 weeks as well as after a 4-week recovery period...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28945024/-pathogenesis-and-treatment-of-insulin-resistance-in-chronic-kidney-disease-and-interventional-effects-of-chinese-herbal-medicine
#20
REVIEW
Wei Wu, Jing-Jing Yang, Yi-Gang Wan, Yue Tu, Ge Shi, Wen-Bei Han, Bu-Hui Liu, Jian Yao
The kidney is the target organ of insulin with abundant insulin receptors. Thereinto,the renal intrinsic cells including glomerular podocytes,endothelial cells,mesangial cells,renal tubular epitheliums and collecting duct epithelial cells are all highly sensitive to insulin as the effector cells. Furthermore,the structural and functional abnormalities of these cells are closely related to insulin and its receptors activity. It is reported that the chronic kidney disease(CKD)patients have systemic or renal insulin resistance(IR)...
January 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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