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https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#1
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/28414128/impaired-degradation-of-medullary-wnk4-in-the-kidneys-of-klhl2-knockout-mice
#2
Yuri Kasagi, Daiei Takahashi, Tomomi Aida, Hidenori Nishida, Naohiro Nomura, Moko Zeniya, Takayasu Mori, Emi Sasaki, Fumiaki Ando, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and Cullin3 (CUL3) genes were identified as being responsible for hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII). Normally, the KLHL3/CUL3 ubiquitin ligase complex degrades WNKs. In PHAII, the loss of interaction between KLHL3 and WNK4 increases levels of WNKs because of impaired ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC cascade in the kidney's distal convoluted tubules (DCT)...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28409341/zebrafish-pronephros-development
#3
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
#4
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/28408205/temporal-spatial-and-phenotypical-changes-of-pdgfr%C3%AE-expressing-fibroblasts-during-late-lung-development
#5
Mehari Endale, Shawn Ahlfeld, Erik Bao, Xiaoting Chen, Jenna Green, Zach Bess, Matthew T Weirauch, Yan Xu, Anne Karina Perl
Many studies have investigated the source and role of epithelial progenitors during lung development; such information is limited for fibroblast populations and their complex role in the developing lung. In this study, we characterized the spatial location, mRNA expression and Immunophenotyping of PDGFRα(+) fibroblasts during sacculation and alveolarization. Confocal microscopy identified spatial association of PDGFRα expressing fibroblasts with proximal epithelial cells of the branching bronchioles and the dilating acinar tubules at E16...
April 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28395333/ovine-uterine-space-restriction-causes-dysregulation-of-the-renin-angiotensin-system-in-fetal-kidneys%C3%A2
#6
Rachel A Kranch-Shorthouse, Adam S Bauer, Ronald R Magness, Gladys E Lopez, Jeffrey L Segar, Sharon E Blohowiak, Pamela J Kling
In ovine pregnancy, uterine space restriction (USR) resulting from decreased space for placental attachment caused intrauterine growth restriction and impaired nephrogenesis. The fetal kidney renin-angiotensin system (RAS) is involved in nephrogenesis, fluid balance, and iron deposition. Angiotensin II exerts its effects via multiple receptors: angiotensin II 1-8 receptor type 1 (AT 1 R) and type 2 (AT 2 R), and angiotensin II 1-7 Mas receptor (MASR). Objective: : To test the hypothesis that ovine USR is associated with dysregulation of the fetal renal RAS...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28390426/successful-treatment-of-early-allograft-dysfunction-with-cinacalcet-in-a-patient-with-nephrocalcinosis-caused-by-severe-hyperparathyroidism-a-case-report
#7
Boonyarit Cheunsuchon, Suchai Sritippayawan
BACKGROUND: Hyperparathyroidism is common in patients undergoing kidney transplantation. Occasionally, this condition can cause early allograft dysfunction by inducing calcium phosphate deposition in the allograft, which results in nephrocalcinosis. Although nephrocalcinosis occurs occasionally in kidney allografts, it has only rarely been reported in the literature. CASE PRESENTATION: Here, we present the case of a 58-year-old Thai woman with severe hyperparathyroidism who received a living-related kidney transplant from her 35-year-old son...
April 8, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28375568/fludrocortisone-therapy-for-persistent-hyperkalaemia
#8
S J H Dobbin, J R Petrie, M E J Lean, G A McKay
Hyperkalaemia is often seen in individuals with renal impairment and may be exacerbated, particularly in diabetic nephropathy, by hyporeninaemic aldosterone deficiency (type 4 renal tubular acidosis) which may, in turn, be caused or complicated by chronic interstitial nephritis or drug therapy (Table 1). Fludrocortisone is a synthetic corticosteroid with mineralocorticoid activity that increases sodium resorption and promotes potassium excretion in the distal convoluted renal tubule. It therefore seems a logical option to reverse hyperkalaemia in type 4 renal tubular acidosis; however, we can find no published guideline recommending this use [1,2]...
April 4, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28373577/parathyroid-hormone-controls-paracellular-ca-2-transport-in-the-thick-ascending-limb-by-regulating-the-tight-junction-protein-claudin14
#9
Tadatoshi Sato, Marie Courbebaisse, Noriko Ide, Yi Fan, Jun-Ichi Hanai, Jovana Kaludjerovic, Michael J Densmore, Quan Yuan, Hakan R Toka, Martin R Pollak, Jianghui Hou, Beate Lanske
Renal Ca(2+) reabsorption is essential for maintaining systemic Ca(2+) homeostasis and is tightly regulated through the parathyroid hormone (PTH)/PTHrP receptor (PTH1R) signaling pathway. We investigated the role of PTH1R in the kidney by generating a mouse model with targeted deletion of PTH1R in the thick ascending limb of Henle (TAL) and in distal convoluted tubules (DCTs): Ksp-cre;Pth1r(fl/fl) Mutant mice exhibited hypercalciuria and had lower serum calcium and markedly increased serum PTH levels. Unexpectedly, proteins involved in transcellular Ca(2+) reabsorption in DCTs were not decreased...
April 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28366875/dual-role-of-muc1-mucin-in-kidney-ischemia-reperfusion-injury-nephroprotector-in-early-phase-but-pro-fibrotic-in-late-phase
#10
Jean-Baptiste Gibier, Brigitte Hémon, Mélanie Fanchon, Kelly Gaudelot, Nicolas Pottier, Bélinda Ringot, Isabelle Van Seuningen, François Glowacki, Christelle Cauffiez, David Blum, Marie-Christine Copin, Michaël Perrais, Viviane Gnemmi
Acute kidney injury (AKI) is characterized by acute tubular necrosis (ATN) which involves mainly proximal tubules. Past AKI is associated with higher risk of chronic kidney disease (CKD). The MUC1 mucin is a large glycoprotein responsible for epithelial protection and locates to convoluted distal tubules and collecting ducts. Since MUC1 activates the epithelial-mesenchymal transition (EMT) in carcinoma cells, we hypothesized that MUC1 could be involved in epithelial tubular cell plasticity, a process that accompanies epithelial repair, but also participates into kidney fibrosis, histological substratum of CKD...
March 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28365586/enac-and-romk-activity-are-inhibited-in-the-dct2-cnt-of-tgwnk4-phaii-mice
#11
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
#12
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
https://www.readbyqxmd.com/read/28359809/wnt8a-expands-the-pool-of-embryonic-kidney-progenitors-in-zebrafish
#13
Richard W Naylor, Hwa In Han, Neil A Hukriede, Alan J Davidson
During zebrafish embryogenesis the pronephric kidney arises from a small population of posterior mesoderm cells that then undergo expansion during early stages of renal organogenesis. While wnt8 is required for posterior mesoderm formation during gastrulation, it is also transiently expressed in the post-gastrula embryo in the intermediate mesoderm, the precursor to the pronephros and some blood/vascular lineages. Here, we show that knockdown of wnt8a, using a low dose of morpholino that does not disrupt early mesoderm patterning, reduces the number of kidney and blood cells...
March 27, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28356293/urinary-dcr2-is-a-novel-biomarker-for-tubulointerstitial-injury-in-patients-with-diabetic-nephropathy
#14
Jia Chen, Wei-Wei Zhang, Ke-Hong Chen, Li-Rong Lin, Huan-Zi Dai, Kai-Long Li, Jian-Guo Zhang, Lu-Quan Zheng, Bi-Qiong Fu, Ya-Ni He
Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients which diagnosed by renal biopsy. uDcR2 levels were measured by ELISA and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2, renal functional parameters were evaluated...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28356287/pgf2%C3%AE-regulates-the-basolateral-k-channels-in-the-distal-convoluted-tubule-dct
#15
Lijun Wang, Chengbiao Zhang, Xiao-Tong Su, Dao-Hong Lin, Peng Wu, Michal Laniado Schwartzman, Wen-Hui Wang
We aim to examine the role of PGF2α receptor (FP), a highly expressed prostaglandin receptor in the DCT, in regulating basolateral 40 pS K channel. The single channel studies demonstrated that PGF2α had a biphasic effect on the 40 pS K channel in the DCT: PGF2α stimulated at low concentrations (less than 500 nM) while at high concentrations (above 1µM) it inhibited the 40 pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF2α (a metabolite of PGF2α) nor PGE2 was able to mimic the effect of PGF2α on the 40 pS K channel in the DCT...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28349219/bacterial-colonization-in-the-apical-part-of-extracted-human-teeth-following-root-end-resection-and-filling-a-confocal-laser-scanning-microscopy-study
#16
Igor Tsesis, Shlomo Elbahary, Nuphar Blau Venezia, Eyal Rosen
OBJECTIVES: The purpose of this study was to evaluate Enterococcus faecalis colonization at the apical part of root canals following root-end resection and filling using confocal laser scanning microscopy (CLSM). MATERIALS AND METHODS: The apical 3-mm root-ends of 55 extracted single rooted human teeth were resected, and 3-mm retrograde cavities were prepared and filled using either mineral trioxide aggregate (MTA), intermediate restorative material (IRM), or Biodentine (n = 10 each); 25 teeth served as controls...
March 28, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28341694/mineralocorticoid-receptor-and-nacl-transport-mechanisms-in-the-renal-distal-nephron
#17
Shigeru Shibata
A key role of aldosterone and mineralocorticoid receptor is to regulate fluid volume and K+ homeostasis in the body by acting on the renal distal nephron. Global responses of the kidney to elevated aldosterone levels are determined by the coordinate action of different constituent tubule cells, including principal cells, intercalated cells, and distal convoluted tubule cells. Recent studies on genetic mutations causing aldosterone overproduction have identified molecules involved in aldosterone biosynthesis in the adrenal gland, and there is also increasing evidence for mechanisms and signaling pathways regulating the balance between renal NaCl reabsorption and K+ secretion, the two major effects of aldosterone...
March 24, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#18
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevation in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28322790/short-chain-fatty-acids-gpr41-and-gpr43-ligands-inhibit-tnf-%C3%AE-induced-mcp-1-expression-by-modulating-p38-and-jnk-signaling-pathways-in-human-renal-cortical-epithelial-cells
#19
Mamiko Kobayashi, Daisuke Mikami, Hideki Kimura, Kazuko Kamiyama, Yukie Morikawa, Seiji Yokoi, Kenji Kasuno, Naoki Takahashi, Takanobu Taniguchi, Masayuki Iwano
Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced predominantly by gut microbiota fermentation of dietary fiber. SCFAs are newly identified as endogenous ligands of two orphan G protein-coupled receptors, GPR41 and GPR43, which have the potential to modulate inflammation. Therefore, GPR41 and GPR43 may mediate the link between the gut microbiome status and various disease conditions including renal inflammation. This study aimed at investigating whether SCFAs activate GPR41 and GPR43, and thereby exert anti-inflammatory effects in human renal cortical epithelial cells (HRCEs) as a main component of kidney tissue...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28317878/kidney-specific-transposon-mediated-gene-transfer-in-vivo
#20
Lauren E Woodard, Jizhong Cheng, Richard C Welch, Felisha M Williams, Wentian Luo, Leslie S Gewin, Matthew H Wilson
Methods enabling kidney-specific gene transfer in adult mice are needed to develop new therapies for kidney disease. We attempted kidney-specific gene transfer following hydrodynamic tail vein injection using the kidney-specific podocin and gamma-glutamyl transferase promoters, but found expression primarily in the liver. In order to achieve kidney-specific transgene expression, we tested direct hydrodynamic injection of a DNA solution into the renal pelvis and found that luciferase expression was strong in the kidney and absent from extra-renal tissues...
March 20, 2017: Scientific Reports
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