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https://www.readbyqxmd.com/read/28724608/erbb4-deletion-accelerates-renal-fibrosis-following-renal-injury
#1
Fenghua Zeng, Tomoki Miyazawa, Lance A Kloepfer, Raymond C Harris
Tubulointerstitial fibrosis (TIF) is a prominent factor in the progression of chronic kidney disease (CKD) regardless of etiology. ErbB4 expression levels were inversely correlated to renal fibrosis in human fibrotic kidneys. In both unilateral ureteral obstruction (UUO) and ischemia reperfusion injury followed by uninephrectomy (IRI/UNx) mouse models, expression levels of ErbB4 were elevated in the early stage of renal injury. Using mice with global ErbB4 deletion except for transgenic rescue in cardiac tissue (ErbB4-/-ht+), we determined that UUO induced similar injury in proximal tubules compared to wild-type mice but more severe injury in distal nephrons...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28705707/gata3-as-a-valuable-marker-to-distinguish-clear-cell-papillary-renal-cell-carcinomas-from-morphologic-mimics
#2
Jose G Mantilla, Tatjana Antic, Maria Tretiakova
Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade, indolent neoplasm, with no reported cases of death from disease or metastasis. These lesions can show clinical, morphologic and immunophenotypic overlap with several aggressive forms of renal cell carcinoma (RCC), including clear cell (CCRCC), translocation RCC and papillary RCC (PRCC) with cytoplasmic clearing. Given the difference in behavior, it is important to reliably separate these entities. We retrospectively reviewed 47 tumors from 45 patients with morphologic features of CCPRCC...
July 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/28695400/role-of-collecting-duct-renin-in-the-pathogenesis-of-hypertension
#3
REVIEW
Alexis A Gonzalez, Lucienne S Lara, Minolfa C Prieto
The presence of renin production by the principal cells of the collecting duct has opened new perspectives for the regulation of intrarenal angiotensin II (Ang II). Angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are present in the tubular fluid coming from the proximal tubule and collecting duct. All the components needed for Ang II formation are present along the nephron, and much is known about the mechanisms regulating renin in juxtaglomerular cells (JG); however, those in the collecting duct remain unclear...
August 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28679296/pharmacological-targeting-of-spak-kinase-in-disorders-of-impaired-epithelial-transport
#4
Jinwei Zhang, Jason K Karimy, Eric Delpire, Kristopher T Kahle
The mammalian SPS1-related proline/alanine-rich serine-threonine kinase SPAK (STK39) modulates ion transport across and between epithelial cells in response to environmental stimuli such osmotic stress and inflammation. Research over the last decade has established a central role for SPAK in the regulation of ion and water transport in the distal nephron, colonic crypts, and pancreatic ducts, and has implicated deregulated SPAK signaling in NaCl-sensitive hypertension, ulcerative colitis and Crohn's disease, and cystic fibrosis...
July 12, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28667491/sglt-2-inhibitors-in-heart-failure-implications-for-the-kidneys
#5
REVIEW
Frederik H Verbrugge, Pieter Martens, Wilfried Mullens
PURPOSE OF REVIEW: This review aims to summarize the renal effects of sodium-glucose transporter-2 (SGLT-2) inhibitors and their potential implications in heart failure pathophysiology. RECENT FINDINGS: In patients with diabetes and established atherosclerosis, the SGLT-2 inhibitor empagliflozin versus placebo significantly reduced the rate of heart failure admissions with 35%. Moreover, empagliflozin slowed kidney disease progression and reduced the need for renal replacement therapy...
June 30, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28656378/comparative-transcriptomic-analysis-identifies-evolutionarily-conserved-gene-products-in-the-vertebrate-renal-distal-convoluted-tubule
#6
REVIEW
Yuya Sugano, Chiara Cianciolo Cosentino, Dominique Loffing-Cueni, Stephan C F Neuhauss, Johannes Loffing
Understanding the molecular basis of the complex regulatory networks controlling renal ion transports is of major physiological and clinical importance. In this study, we aimed to identify evolutionarily conserved critical players in the function of the renal distal convoluted tubule (DCT) by a comparative transcriptomic approach. We generated a transgenic zebrafish line with expression of the red fluorescent mCherry protein under the control of the zebrafish DCT-specific promoter of the thiazide-sensitive NaCl cotransporter (NCC)...
June 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28646163/aldosterone-modulates-the-association-between-ncc-and-enac
#7
Brandi M Wynne, Abinash C Mistry, Otor Al-Khalili, Rickta Mallick, Franziska Theilig, Douglas C Eaton, Robert S Hoover
Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636485/mineralocorticoids-modulate-the-expression-of-the-%C3%AE-3-subunit-of-the-na-k-atpase-in-the-renal-collecting-duct
#8
Macarena Rojas, Pablo Díaz, Pablo León, Alexis A Gonzalez, Magdalena González, Víctor Barrientos, Nikolay B Pestov, Rodrigo Alzamora, Luis Michea
Renal sodium reabsorption depends on the activity of the Na(+),K(+)-ATPase α/β heterodimer. Four α (α1-4) and 3 β (β1-3) subunit isoforms have been described. It is accepted that renal tubule cells express α1/β1 dimers. Aldosterone stimulates Na(+),K(+)-ATPase activity and may modulate α1/β1 expression. However, some studies suggest the presence of β3 in the kidney. We hypothesized that the β3 isoform of the Na(+),K(+)-ATPase is expressed in tubular cells of the distal nephron, and modulated by mineralocorticoids...
June 21, 2017: Channels
https://www.readbyqxmd.com/read/28634265/30-years-of-the-mineralocorticoid-receptor-coregulators-as-mediators-of-mineralocorticoid-receptor-signalling-diversity
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28537051/artificial-ureter-in-patients-with-extensive-ureteral-damage
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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