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Distal Nephron

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https://www.readbyqxmd.com/read/28634265/30-years-of-the-mineralocorticoid-receptor-coregulators-as-mediators-of-mineralocorticoid-receptor-signalling-diversity
#1
REVIEW
Peter J Fuller, Jun Yang, Morag J Young
The cloning of the mineralocorticoid receptor (MR) 30 years ago was the start of a new era of research into the regulatory processes of MR signalling at target genes in the distal nephron, and subsequently in many other tissues. Nuclear receptor (NR) signalling is modified by interactions with coregulatory proteins that serve to enhance or inhibit the gene transcriptional responses. Over 400 coregulatory proteins have been described for the NR super family, many with functional roles in signalling, cellular function, physiology and pathophysiology...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28614118/the-renal-response-to-potassium-stress-integrating-past-with-present
#2
Cary R Boyd-Shiwarski, Arohan R Subramanya
PURPOSE OF REVIEW: The current review combines past findings with recent advances in our understanding of the homeostatic response to potassium imbalance. RECENT FINDINGS: Following the ingestion of a dietary potassium load, a combination of extrarenal and renal mechanisms act to maintain extracellular K+ within a tight window. Through hormonal regulation and direct K+ sensing, the nephron is ideally suited to respond to wide shifts in external K+ balance. Current evidence indicates that dietary K+ loading triggers a coordinated kaliuretic response that appears to involve voltage-dependent changes in sodium transport across multiple nephron segments, including the proximal tubule, medullary loop of Henle, and distal tubule...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28604611/eplerenone-resistant-salt-sensitive-hypertension-in-nedd4-2-c2-ko-mice
#3
Tabito Kino, Tomoaki Ishigami, Tsumugi Murata, Hiroshi Doi, Rie Nakashima-Sasaki, Lin Chen, Michiko Sugiyama, Kengo Azushima, Hiromichi Wakui, Shintaro Minegishi, Kouichi Tamura
The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake...
June 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28577072/regulation-of-renal-na-k-cl-cotransporters-by-vasopressin
#4
REVIEW
Sebastian Bachmann, Kerim Mutig
Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption...
June 2, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28566500/gender-difference-in-electrolyte-transport-i-role-of-at1a-receptor-in-thiazide-sensitive-na-cl-cotransporter-activity-and-expression-in-male-and-female-mice
#5
Jing Li, Ryo Hatano, Shuhua Xu, Laxiang Wan, Lei Yang, Alan M Weinstein, Lawrence G Palmer, Tong Wang
We studied gender differences in NCC activity and expression in wild-type (WT) and AT1a receptor knockout (KO) mice. In renal clearance experiments, urine volume (UV), GFR, absolute Na and K (ENa; EK) and fractional Na and K (FENa; FEK) excretion were measured and compared at peak changes after bolus iv injection of hydrochlorothiazide (HCTZ; 30mg/kg). In WT, females responded more strongly than males to HCTZ, with larger fractional increases of UV (7.8- vs. 3.4-fold), ENa (11.7- vs. 5.7-fold), FENa (7.9-vs...
May 31, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28552604/evidence-of-in%C3%A2-vitro-preservation-of-human-nephrogenesis-at-the-single-cell-level
#6
Naomi Pode-Shakked, Rotem Gershon, Gal Tam, Dorit Omer, Yehudit Gnatek, Itamar Kanter, Sarit Oriel, Guy Katz, Orit Harari-Steinberg, Tomer Kalisky, Benjamin Dekel
During nephrogenesis, stem/progenitor cells differentiate and give rise to early nephron structures that segment to proximal and distal nephron cell types. Previously, we prospectively isolated progenitors from human fetal kidney (hFK) utilizing a combination of surface markers. However, upon culture nephron progenitors differentiated and could not be robustly maintained in vitro. Here, by culturing hFK in a modified medium used for in vitro growth of mouse nephron progenitors, and by dissection of NCAM(+)/CD133(-) progenitor cells according to EpCAM expression (NCAM(+)/CD133(-)/EpCAM(-), NCAM(+)/CD133(-)/EpCAM(dim), NCAM(+)/CD133(-)/EpCAM(bright)), we show at single-cell resolution a preservation of uninduced and induced cap mesenchyme as well as a transitioning mesenchymal-epithelial state...
May 25, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28537051/artificial-ureter-in-patients-with-extensive-ureteral-damage
#7
Mohammad Yazdani, Amir Javid, Mehrdad Mohammadi Sichani, Mohammad Reza Gharaati, Emad Yazdani
PURPOSE: loss of significant lengths of ureter when substitution with bowel or bladder fails is a disaster in urology. This study is conducted to evaluate the results of subcutaneous nephron-vesical bypass (SNVB) in ureteral damage of different etiologies. MATERIALS AND METHODS: Seventeen SNVB were employed in patients with ureteral injuries. We employed a device consisted of an internal silicone tube covered by a coiled PTFE tube to replace the ureter. This is called artificial ureter (AU)...
May 23, 2017: Urology Journal
https://www.readbyqxmd.com/read/28507171/first-in-man-demonstration-of-direct-endothelin-mediated-natriuresis-and-diuresis
#8
Robert W Hunter, Rebecca Moorhouse, Tariq E Farrah, Iain M MacIntyre, Takae Asai, Peter J Gallacher, Debbie Kerr, Vanessa Melville, Alicja Czopek, Emma E Morrison, Jess R Ivy, James W Dear, Matthew A Bailey, Jane Goddard, David J Webb, Neeraj Dhaun
Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1...
May 15, 2017: Hypertension
https://www.readbyqxmd.com/read/28501304/speculations-on-salt-and-the-genesis-of-arterial-hypertension
#9
REVIEW
Jens Titze, Friedrich C Luft
Blood pressure salt sensitivity and salt resistance are mechanistically imperfectly explained. A prescient systems medicine approach by Guyton and colleagues-more than 50 years ago-suggested how salt intake might influence blood pressure. They proposed that a high-salt diet engenders sodium accumulation, volume expansion, cardiac output adjustments, and then autoregulation for flow maintenance. The autoregulation in all vascular beds increases systemic vascular resistance, causing the kidneys to excrete more salt and water, thus reducing systems to normal and minimizing any changes in blood pressure...
June 2017: Kidney International
https://www.readbyqxmd.com/read/28493961/aldosterone-signaling-regulates-the-over-expression-of-claudin-4-and-8-at-the-distal-nephron-from-type-1-diabetic-rats
#10
Eduardo Molina-Jijón, Rafael Rodríguez-Muñoz, Ricardo González-Ramírez, Carmen Namorado-Tónix, José Pedraza-Chaverri, Jose L Reyes
Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3-21. Twenty-one days after STZ injection the rats were sacrificed...
2017: PloS One
https://www.readbyqxmd.com/read/28480774/endoscopic-management-of-upper-tract-urothelial-carcinoma
#11
REVIEW
Jay D Raman, Rosa Park
Radical nephroureterectomy with an ipsilateral bladder cuff is the referent standard for management of muscle-invasive, high-grade, or bulky upper-tract urothelial carcinoma (UTUC). Nonetheless, certain patients with UTUC have imperative or elective indications for kidney preservation thereby lending to more conservative strategies for management of this disease. Areas covered: A review of the PubMED and Medline databases was performed to identify original scientific and review articles discussing retrograde ureteroscopic or percutaneous antegrade resection of UTUC tumors published between 1995 and 2016...
June 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28454724/protein-phosphatase-1%C3%AE-enhances-renal-aldosterone-signaling-via-mineralocorticoid-receptor-stabilization
#12
Shunmugam Nagarajan, Twinkle Vohra, Johannes Loffing, Nourdine Faresse
Stimulation of the mineralocorticoid receptor (MR) by aldosterone controls several physiological parameters including blood pressure, inflammation or metabolism. We previously showed that MR turnover constitutes a crucial regulatory step in the responses of renal epithelial cells to aldosterone. Here, we identified Protein Phosphatase 1 alpha (PP1α), as a novel cytoplasmic binding partner of MR that promotes the receptor activity. The RT-PCR expression mapping of PP1α reveals a high expression in the kidney, particularly in the distal part of the nephron...
April 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28445401/tradeoff-in-the-nephron-a-theory-to-explain-the-primacy-of-phosphate-in-the-pathogenesis-of-secondary-hyperparathyroidism
#13
Kenneth R Phelps
Chronic kidney disease (CKD) causes secondary hyperparathyroidism (SHPT). The cardinal features of SHPT are persistence of normocalcemia as CKD progresses and dependence of the parathyroid hormone concentration ([PTH]) on phosphate influx (IP). The tradeoff-in-the-nephron hypothesis integrates these features. It states that as the glomerular filtration rate (GFR) falls, the phosphate concentration ([P]CDN) rises in the cortical distal nephron, the calcium concentration ([Ca]CDN) in that segment falls, and [PTH] rises to maintain normal calcium reabsorption per volume of filtrate (TRCa/GFR)...
April 26, 2017: Nutrients
https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#14
P Richard Grimm, Richard Coleman, Eric Delpire, Paul A Welling
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK)...
April 25, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28409346/development-and-diseases-of-the-collecting-duct-system
#15
Lihe Chen, Paul J Higgins, Wenzheng Zhang
The collecting duct of the mammalian kidney is important for the regulation of extracellular volume, osmolarity, and pH. There are two major structurally and functionally distinct cell types: principal cells and intercalated cells. The former regulates Na(+) and water homeostasis, while the latter participates in acid-base homeostasis. In vivo lineage tracing using Cre recombinase or its derivatives such as CreGFP and CreER(T2) is a powerful new technique to identify stem/progenitor cells in their native environment and to decipher the origins of the tissue that they give rise to...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28409341/zebrafish-pronephros-development
#16
Richard W Naylor, Sarah S Qubisi, Alan J Davidson
The pronephros is the first kidney type to form in vertebrate embryos. The first step of pronephrogenesis in the zebrafish is the formation of the intermediate mesoderm during gastrulation, which occurs in response to secreted morphogens such as BMPs and Nodals. Patterning of the intermediate mesoderm into proximal and distal cell fates is induced by retinoic acid signaling with downstream transcription factors including wt1a, pax2a, pax8, hnf1b, sim1a, mecom, and irx3b. In the anterior intermediate mesoderm, progenitors of the glomerular blood filter migrate and fuse at the midline and recruit a blood supply...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28408636/aldosterone-regulates-a-5-variant-sgk1-transcript-via-a-shared-hormone-response-element-in-the-sgk1-5-regulatory-region
#17
Nandita S Raikwar, Christie P Thomas
We previously identified a 5' variant alternate transcript of Sgk1 (Sgk1_v3) encoding an NH2-terminal variant Sgk1 isoform, Sgk1_i3 that, like Sgk1, is expressed in the distal convoluted tubule, connecting tubule and collecting duct and can stimulate epithelial Na(+) transport (Am J Physiol Renal Physiol 303: F1527-F1533, 2012). We now demonstrate that, similar to Sgk1, aldosterone and glucocorticoids stimulate Sgk1_v3 expression in cell lines from the collecting duct and airway epithelia. In mice, short term aldosterone infusion and maneuvers that increase endogenous aldosterone secretion including dietary Na(+) deprivation and K(+) loading increases distal nephron Sgk1_v3 expression in vivo...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28389525/role-of-renal-transporters-and-novel-regulatory-interactions-in-the-tal-that-control-blood-pressure
#18
REVIEW
Lesley A Graham, Anna F Dominiczak, Nicholas R Ferreri
Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year. Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney's reabsorption of sodium (Na(+)) relies on sequential actions at various segments along the nephron...
May 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28365586/enac-and-romk-activity-are-inhibited-in-the-dct2-cnt-of-tgwnk4-phaii-mice
#19
Chengbiao Zhang, Lijun Wang, Xiao-Tong Su, Junhui Zhang, Dao-Hong Lin, Wen-Hui Wang
Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4(PHAII)) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl cotransporter (NCC). This leads to decreasing Na(+) delivery to the distal nephron segment including late distal convoluted tubule (DCT) and connecting tubule (CNT). Since epithelial Na(+) channel (ENaC) and renal outer medullary K(+) channel (ROMK or Kir4.1) are expressed in the late DCT and play an important role in mediating K(+) secretion, the aim of the present study is to test whether ROMK and ENaC activity in the DCT/CNT are also compromised in the mice expressing PHAII mutant Wnk4...
April 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28361319/making-a-kidney-organoid-using-the-directed-differentiation-of-human-pluripotent-stem-cells
#20
Minoru Takasato, Melissa H Little
An organoid can be defined as a three-dimensional organ-like structure formed from organ-specific progenitor cells. Organ progenitor cells were empirically found to self-organize three-dimensional tissues when they were aggregated and cultivated in vitro. While this nature power of progenitor cells has an amazing potential to recreate artificial organs in vitro, there had been difficulty to apply this technology to human organs due to the inaccessibility to human progenitor cells until human-induced pluripotent stem cell (hiPSC) was invented by Takahashi and Yamanaka in 2007...
2017: Methods in Molecular Biology
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