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https://www.readbyqxmd.com/read/28656379/physiology-and-pathophysiology-of-the-plasminogen-system-in-the-kidney
#1
REVIEW
Per Svenningsen, Gitte Rye Hinrichs, Rikke Zachar, Rikke Ydegaard, Boye L Jensen
The plasminogen system is important for fibrinolysis in addition to tissue remodeling and inflammation with significance for kidney disease. The system consists of the circulating zymogen plasminogen (Plg) and the tissue- and urokinase-type plasminogen activators, tPA and uPA, expressed in the glomeruli, endothelium and tubular epithelium, respectively, and the inhibitors α2-antiplasmin and plasminogen activator inhibitor-type1, PAI-1. Plasminogen is activated by surface receptors, some with renal expression: urokinase-type plasminogen activator receptor (uPAR), plasminogen receptor KT (Plg-RKT), and tPA, most evident in the endothelium...
June 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28622163/novel-roles-for-mucin-1-in-the-kidney
#2
Mohammad M Al-Bataineh, Rebecca P Hughey
PURPOSE OF REVIEW: Recent studies in the kidney have revealed that the well characterized tumor antigen mucin 1 (MUC1/Muc1) also has numerous functions in the normal and injured kidney. RECENT FINDINGS: Mucin 1 is a transmembrane mucin with a robust glycan-dependent apical targeting signal and efficient recycling from endosomes. It was recently reported that the TRPV5 calcium channel is stabilized on the cell surface by galectin-dependent cross-linking to mucin 1, providing a novel mechanism for regulation of ion channels and normal electrolyte balance...
June 15, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28618678/re-mucin-1-increases-renal-trpv5-activity-in-vitro-and-urinary-level-associates-with-calcium-nephrolithiasis-in-patients
#3
Dean G Assimos
No abstract text is available yet for this article.
July 2017: Journal of Urology
https://www.readbyqxmd.com/read/28614116/parathyroid-hormone-and-the-regulation-of-renal-tubular-calcium-transport
#4
Benjamin Ko
PURPOSE OF REVIEW: Renal tubule excretion of calcium is carefully and complexly regulated. At the center of this process, parathyroid hormone (PTH) is the chief regulator of renal calcium reabsorption. This review outlines our current understanding of PTH's effects on renal tubular calcium transport, focusing on the more recent discoveries beyond its direct regulation of epithelial Ca channel transient receptor potential vanilloid 5 (TRPV5) and looking at its interaction with sodium transport and the hormones fibroblast growth factor 23 (FGF23) and klotho...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28602864/nckx3-was-compensated-by-calcium-transporting-genes-and-bone-resorption-in-a-nckx3-ko-mouse-model
#5
Hyun Yang, Changhwan Ahn, Eun-Kyeong Shin, Ji-Sun Lee, Beum-Soo An, Eui-Bae Jeung
Gene knockout is the most powerful tool for determination of gene function or permanent modification of the phenotypic characteristics of an animal. Existing methods for gene disruption are limited by their efficiency, time required for completion and potential for confounding off-target effects. In this study, a rapid single-step approach to knockout of a targeted gene in mice using zinc-finger nucleases (ZFNs) was demonstrated for generation of mutant (knockout; KO) alleles. Specifically, ZFNs to target the sodium/calcium/potassium exchanger3 (NCKX3) gene in C57bl/6j were designed using the concept of this approach...
June 7, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28600880/klotho-lacks-an-fgf23-independent-role-in-mineral-homeostasis
#6
Olena Andrukhova, Jessica Bayer, Christiane Schüler, Ute Zeitz, Sathish K Murali, Sibel Ada, Jose M Alvarez-Pez, Alina Smorodchenko, Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating vitamin D hormone production and renal handling of minerals by signaling through an FGF receptor/αKlotho (Klotho) receptor complex. Whether Klotho has FGF23-independent effects on mineral homeostasis is a controversial issue. Here, we aimed to shed more light on this controversy by comparing male and female triple knockout mice with simultaneous deficiency in Fgf23 and Klotho and a nonfunctioning vitamin D receptor (VDR) (Fgf23/Klotho/VDR) with double (Fgf23/VDR, Klotho/VDR, and Fgf23/Klotho) and single Fgf23, Klotho, and VDR mutants...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28539338/expression-of-trans-and-paracellular-calcium-and-magnesium-transport-proteins-in-renal-and-intestinal-epithelia-during-lactation
#7
Megan R Beggs, Ida Appel, Per Svenningsen, Karsten Skjødt, R Todd Alexander, Henrik Dimke
Significant alterations in maternal calcium (Ca2+) and magnesium (Mg2+) balance occur during lactation. Ca2+ is the primary divalent cation mobilized into breast milk by demineralization of the skeleton and alterations in intestinal and renal Ca2+ transport. Mg2+ is also concentrated in breast milk, but the underlying mechanisms are not well understood. To determine the molecular alterations in Ca2+ and Mg2+ transport in the intestine and kidney during lactation, 3 groups of female mice consisting of either non-pregnant controls, lactating mice, or mice undergoing involution were examined...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28535500/transient-receptor-potential-vanilloid-5-mediates-ca2-influx-and-inhibits-chondrocyte-autophagy-in-a-rat-osteoarthritis-model
#8
Yingliang Wei, Yanfang Wang, Yutong Wang, Lunhao Bai
BACKGROUND: Autophagy, a self-protective mechanism of chondrocytes, has become a promising target to impede the progress of osteoarthritis (OA). Autophagy is regulated by cytosolic Ca2+ activity and may thus be modified by the Ca2+ permeable transient receptor potential channel vanilloid 5 (TRPV5). Therefore, we investigated the potential role of TRPV5 in mediating Ca2+ influx and in inhibiting chondrocyte autophagy in a rat OA model. METHODS: The rat OA model was assessed by macroscopic and histological analyses...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534087/interspecies-differences-in-pth-mediated-pka-phosphorylation-of-the-epithelial-calcium-channel-trpv5
#9
Mark K van Goor, Sjoerd Verkaart, Teunis J van Dam, Martijn A Huynen, Jenny van der Wijst
The epithelial calcium (Ca(2+)) channel TRPV5 (transient receptor potential vanilloid 5) is expressed in the distal convoluted tubule of the kidney and facilitates active Ca(2+) reabsorption. This process is instrumental for the maintenance of Ca(2+) homeostasis. Therefore, all aspects of TRPV5 function are tightly regulated by the calciotropic parathyroid hormone (PTH). Rabbit (rb)TRPV5 channel activity was shown to be stimulated upon PTH-mediated protein kinase A (PKA) phosphorylation. Since there is incomplete conservation of the PKA consensus motif (RR/QxT) across species, the aim of this study was to extend these findings to humans and characterize the expression and function of human (h)TRPV5...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28374795/a-gate-hinge-controls-the-epithelial-calcium-channel-trpv5
#10
Jenny van der Wijst, Elizabeth H Leunissen, Maxime G Blanchard, Hanka Venselaar, Sjoerd Verkaart, Candice E Paulsen, René J Bindels, Joost G Hoenderop
TRPV5 is unique within the large TRP channel family for displaying a high Ca(2+) selectivity together with Ca(2+)-dependent inactivation. Our study aims to uncover novel insights into channel gating through in-depth structure-function analysis. We identify an exceptional tryptophan (W583) at the terminus of the intracellular pore that is unique for TRPV5 (and TRPV6). A combination of site-directed mutagenesis, biochemical and electrophysiological analysis, together with homology modeling, demonstrates that W583 is part of the gate for Ca(2+) permeation...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28107527/effects-of-the-administration-of-25-oh-vitamin-d3-in-an-experimental-model-of-chronic-kidney-disease-in-animals-null-for-1-alpha-hydroxylase
#11
Noelia Torremadé, Milica Bozic, David Goltzman, Elvira Fernandez, José M Valdivielso
The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals...
2017: PloS One
https://www.readbyqxmd.com/read/28066924/side-chain-flexibility-and-coupling-between-the-s4-s5-linker-and-the-trp-domain-in-thermo-sensitive-trp-channels-insights-from-protein-modeling
#12
Sergio Romero-Romero, Froylan Gomez Lagunas, Daniel Balleza
The transient receptor potential (TRP) superfamily is subdivided into several subfamilies on the basis of sequence similarity, which is highly heterogeneous but shows a molecular architecture that resembles the one present in members of the Kv channel superfamily. Because of this diversity, they produce a large variety of channels with different gating and permeability properties. Elucidation of these particular features necessarily requires comparative studies based on structural and functional data. The present study aims to compilate, analyze, and determine, in a coherent way, the relationship between intrinsic side-chain flexibility and the allosteric coupling in members of the TRPV, TRPM, and TRPC families...
January 9, 2017: Proteins
https://www.readbyqxmd.com/read/28039038/transient-receptor-potential-vanilloid-6-trpv6-in-the-mouse-brain-distribution-and-estrous-cycle-related-changes-in-the-hypothalamus
#13
Santosh Kumar, Uday Singh, Omprakash Singh, Chandan Goswami, Praful S Singru
Transient receptor potential vanilloid (TRPV) subfamily of cationic channels have emerged as novel players in neural regulation. Unlike other members of TRPV subfamily, TRPV5 and TRPV6 are highly Ca(2+)-selective. Although TRPV5/TRPV6 transcripts are expressed in mouse brain, understanding the full functional spectrum of these ion channels in the brain is however limited due to the lack of information on their neuroanatomical distribution. We have studied TRPV6 in mouse brain in further detail. In the hypothalamus, while Western blot analysis using TRPV6 specific antiserum showed a distinct ∼95 kDa band corresponding to the molecular weight of TRPV6, transcripts for TRPV6 were detected with RT-PCR...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27913205/trp-channels-in-calcium-homeostasis-from-hormonal-control-to-structure-function-relationship-of-trpv5-and-trpv6
#14
REVIEW
Mark K C van Goor, Joost G J Hoenderop, Jenny van der Wijst
Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture...
November 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27751461/re-mucin-1-increases-renal-trpv5-activity-in%C3%A2-vitro-and-urinary-level-associates-with-calcium-nephrolithiasis-in-patients
#15
Dean G Assimos
No abstract text is available yet for this article.
November 2016: Journal of Urology
https://www.readbyqxmd.com/read/27632366/evaluation-and-comparison-of-vitamin-d-responsive-gene-expression-in-ovine-canine-and-equine-kidney
#16
Sara Azarpeykan, Keren E Dittmer, Jonathan C Marshall, Kalyani C Perera, Erica K Gee, Els Acke, Keith G Thompson
The aim of this study was to determine the relative abundance and relationship of vitamin D responsive and calcium transporting transcripts (TRPV5, TRPV6, calD9k, calD28k, PMCA, NCX1, CYP27B1, CYP24A1, and VDR) in ovine, canine and, equine kidney using quantitative real-time PCR (RT-qPCR), and then perform a comparison between the three species. Renal tissue samples were harvested post-mortem from 10 horses, 10 sheep, and five dogs. Primers were designed for each gene. For each sample total RNA was extracted, cDNA synthesised, and RT-qPCR was performed...
2016: PloS One
https://www.readbyqxmd.com/read/27622885/fgf23-klotho-signaling-axis-in-the-kidney
#17
REVIEW
Reinhold G Erben, Olena Andrukhova
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone protecting against the potentially deleterious effects of hyperphosphatemia by suppression of phosphate reabsorption and of active vitamin D hormone synthesis in the kidney. The kidney is one of the main target organs of FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23-Klotho signaling in the kidney. During recent years, it has become clear that FGF23 acts independently on proximal and distal tubular epithelium...
September 10, 2016: Bone
https://www.readbyqxmd.com/read/27469036/is-the-renal-kallikrein-kinin-system-a-factor-that-modulates-calciuria
#18
Armando Luis Negri
Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK)...
July 25, 2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/27409607/regulation-of-intestinal-epithelial-calcium-transport-proteins-by-stanniocalcin-1-in-caco2-cells
#19
Jinmei Xiang, Rui Guo, Chunyun Wan, Liming Wu, Shijin Yang, Dingzong Guo
Stanniocalcin-1 (STC1) is a calcium and phosphate regulatory hormone. However, the exact molecular mechanisms underlying how STC1 affects Ca(2+) uptake remain unclear. Here, the expression levels of the calcium transport proteins involved in transcellular transport in Caco2 cells were examined following over-expression or inhibition of STC1. These proteins include the transient receptor potential vanilloid members (TRPV) 5 and 6, the plasma membrane calcium ATPase 1b (PMCA1b), the sodium/calcium exchanger (NCX1), and the vitamin D receptor (VDR)...
July 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27296226/crystal-structure-of-the-epithelial-calcium-channel-trpv6
#20
Kei Saotome, Appu K Singh, Maria V Yelshanskaya, Alexander I Sobolevsky
Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels...
June 23, 2016: Nature
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