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Distal Nephron

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https://www.readbyqxmd.com/read/28814438/collecting-duct-prorenin-receptor-knockout-reduces-renal-function-increases-na-excretion-and-mitigates-renal-responses-in-angii-induced-hypertensive-mice
#1
Minolfa C Prieto, Virginia Reverte, Mykola Mamenko, Marta Kuczeriska, Luciana C Veiras, Carla B Rosales, Matthew McLellan, Oliver Gentile, V Behrana Jensen, Atsuhiro Ichihara, Alicia A McDonough, Oleh M Pochynyuk, Alexis A Gonzalez
Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANGII-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial...
August 16, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28783044/phenotypic-and-pharmacogenetic-evaluation-of-patients-with-thiazide-induced-hyponatremia
#2
James S Ware, Louise V Wain, Sarath K Channavajjhala, Victoria E Jackson, Elizabeth Edwards, Run Lu, Keith Siew, Wenjing Jia, Nick Shrine, Sue Kinnear, Mahli Jalland, Amanda P Henry, Jenny Clayton, Kevin M O'Shaughnessy, Martin D Tobin, Victor Schuster, Stuart Cook, Ian P Hall, Mark Glover
Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone...
August 7, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28774999/sexual-dimorphic-pattern-of-renal-transporters-and-electrolyte-homeostasis
#3
Luciana C Veiras, Adriana C C Girardi, Joshua Curry, Lei Pei, Donna L Ralph, An Tran, Regiane C Castelo-Branco, Nuria Pastor-Soler, Cristina T Arranz, Alan S L Yu, Alicia A McDonough
Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did...
August 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28771454/%C3%AE-ketoglutarate-drives-electroneutral-nacl-reabsorption-in-intercalated-cells-by-activating-a-g-protein-coupled-receptor-oxgr1
#4
Paul R Grimm, Paul A Welling
PURPOSE OF REVIEW: This review describes the recent discoveries about a powerful electroneutral NaCl reabsorption mechanism in intercalated cells, and its regulation by an intrarenal metabolite paracrine, α-ketoglutartate, and the G-protein coupled receptor, Oxgr1. RECENT FINDINGS: The distal nephron fine-tunes sodium, chloride, potassium, hydrogen, bicarbonate and water transport to maintain electrolyte homeostasis and blood pressure. Intercalated cells have been traditionally viewed as the professional regulators of acid-base balance, but recent studies reveal that a specific population of intercalated cells, identified by the pendrin-transporter, have a surprising role in the regulation of salt balance...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28768768/regulation-of-the-epithelial-na-channel-by-paraoxonase-2
#5
Shujie Shi, Teresa M Buck, Carol L Kinlough, Allison L Marciszyn, Rebecca P Hughey, Martin Chalfie, Jeffrey L Brodsky, Thomas R Kleyman
Paraoxonase-2 (PON-2) is a membrane-bound lactonase with unique anti-oxidative and anti-atherosclerotic properties. PON-2 shares key structural elements with MEC-6, an endoplasmic reticulum resident molecular chaperone in Caenorhabditis elegans MEC-6 modulates the expression of a mechano-transductive ion channel comprised of MEC-4 and MEC-10 in touch receptor neurons. Because pon-2 mRNA resides in multiple rat nephron segments, including aldosterone-sensitive distal nephron where the epithelial Na(+) channel (ENaC) is expressed, we hypothesized that PON-2 would similarly regulate ENaC expression...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28760814/sall1-nurd-interaction-regulates-multipotent-nephron-progenitors-and-is-required-for-loop-of-henle-formation
#6
Jeannine M Basta, Lynn Robbins, Darcy R Denner, Grant R Kolar, Michael Rauchman
The formation of the proper number of nephrons requires a tightly regulated balance between renal progenitor cell self-renewal and differentiation. The molecular pathways that regulate the transition from renal progenitor to renal vesicle are not well understood. Here we show that Sall1interacts with the Nucleosome Remodeling and Deacetylase Complex (NuRD) to inhibit premature differentiation of nephron progenitor cells. Disruption of Sall1-NuRD in vivo in knock-in mice (ΔSRM) resulted in accelerated differentiation of nephron progenitors and bilateral renal hypoplasia...
July 31, 2017: Development
https://www.readbyqxmd.com/read/28760224/hemodynamic-and-renal-implications-of-sodium-glucose-cotransporter-2-inhibitors-in-type-2-diabetes-mellitus
#7
Alberto Tejedor Jorge
In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28750403/ablation-of-the-cl-hco3-exchanger-pendrin-enhances-hydrochlorothiazide-induced-diuresis
#8
Saeed Alshahrani, Manoocher Soleimani
BACKGROUND/AIMS: The Cl-/HCO3- exchanger pendrin and the thiazide-sensitive Na-Cl cotransporter NCC are expressed in the kidney distal nephron and mediate salt absorption. We hypothesized that deletion of pendrin leaves NCC as the major salt absorbing transporter in the distal nephron and therefore enhances salt excretion by hydrochlorothiazide (HCTZ). METHODS: Metabolic cage studies were performed in wild type, pendrin KO and NCC KO mice at baseline and following HCTZ treatment...
July 27, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28750036/generation-and-phenotypic-characterization-of-pde1a-mutant-mice
#9
Xiaofang Wang, Satsuki Yamada, Wells B LaRiviere, Hong Ye, Jason L Bakeberg, María V Irazabal, Fouad T Chebib, Jan van Deursen, Peter C Harris, Caroline R Sussman, Atta Behfar, Christopher J Ward, Vicente E Torres
It has been proposed that a reduction in intracellular calcium causes an increase in intracellular cAMP and PKA activity through stimulation of calcium inhibitable adenylyl cyclase 6 and inhibition of phosphodiesterase 1 (PDE1), the main enzymes generating and degrading cAMP in the distal nephron and collecting duct, thus contributing to the development and progression of autosomal dominant polycystic kidney disease (ADPKD). In zebrafish pde1a depletion aggravates and overexpression ameliorates the cystic phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28747361/metabolic-acidosis-stimulates-the-production-of-the-antimicrobial-peptide-cathelicidin-in-rabbit-urine
#10
Hu Peng, Jeffrey M Purkerson, Andrew L Schwaderer, George J Schwartz
Intercalated cells of the collecting duct (CD) are critical for acid-base homeostasis and innate immune defense of the kidney. Little is known about the impact of acidosis on innate immune defense in the distal nephron. Urinary tract infections are mainly due to Escherichia coli and are an important risk factor for development of chronic kidney disease. While the effect of urinary pH on growth of E. coli is well established, in this study we demonstrate that acidosis increases urine antimicrobial activity due, at least in part, to induction of cathelicidin expression within the CD...
July 26, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28744670/rna-binding-protein-hur-enhances-mineralocorticoid-signaling-in-renal-kc3ac1-cells-under-hypotonicity
#11
Ingrid Lema, Larbi Amazit, Khadija Lamribet, Jérôme Fagart, Anne Blanchard, Marc Lombès, Nadia Cherradi, Say Viengchareun
Mineralocorticoid receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron. Herein, we decipher mechanisms by which hypotonicity increases MR expression in renal principal cells. We identify HuR (human antigen R), an mRNA-stabilizing protein, as an important posttranscriptional regulator of MR expression. Hypotonicity triggers a rapid and reversible nuclear export of HuR in renal KC3AC1 cells, as quantified by high-throughput microscopy. We also identify a key hairpin motif in the 3'-untranslated region of MR transcript, pivotal for the interaction with HuR and its stabilizing function...
July 25, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28724608/erbb4-deletion-accelerates-renal-fibrosis-following-renal-injury
#12
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
#13
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
#14
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
#15
REVIEW
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...
August 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28667491/sglt-2-inhibitors-in-heart-failure-implications-for-the-kidneys
#16
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...
August 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
#17
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)...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28646163/aldosterone-modulates-the-association-between-ncc-and-enac
#18
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
#19
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
#20
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
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