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molecular mechanism,nephron

Abdel A Alli, Ling Yu, Meaghan Rayann Holzworth, Jacob Richards, Kit-Yan Cheng, I Jeanette Lynch, Charles S Wingo, Michelle L Gumz
Circadian rhythms govern physiological functions and are important for overall health. The molecular circadian clock is comprised of several transcription factors that mediate circadian control of physiological function in part by regulating gene expression in a tissue-specific manner. These connections are well established but the underlying mechanisms are incompletely understood. The overall goal of this study was to examine the connection between the circadian clock protein Per1, ENaC, and BP using a multi-pronged approach...
February 13, 2019: American Journal of Physiology. Renal Physiology
Shireen-A Davies, Pablo Cabrero, Richard Marley, Guillermo Martinez Corrales, Saurav Ghimire, Anthony J Dornan, Julian A T Dow
The insect renal (Malpighian) tubule has long been a model system for the study of fluid secretion and its neurohormonal control, as well as studies on ion transport mechanisms. To extend these studies beyond the boundaries of classical physiology, a molecular genetic approach together with the 'omics technologies is required. To achieve this in any vertebrate transporting epithelium remains a daunting task, as the genetic tools available are still relatively unsophisticated. Drosophila melanogaster, however, is an outstanding model organism for molecular genetics...
2019: Methods in Molecular Biology
Andrew P Morris, Thu H Le, Haojia Wu, Artur Akbarov, Peter J van der Most, Gibran Hemani, George Davey Smith, Anubha Mahajan, Kyle J Gaulton, Girish N Nadkarni, Adan Valladares-Salgado, Niels Wacher-Rodarte, Josyf C Mychaleckyj, Nicole D Dueker, Xiuqing Guo, Yang Hai, Jeffrey Haessler, Yoichiro Kamatani, Adrienne M Stilp, Gu Zhu, James P Cook, Johan Ärnlöv, Susan H Blanton, Martin H de Borst, Erwin P Bottinger, Thomas A Buchanan, Sylvia Cechova, Fadi J Charchar, Pei-Lun Chu, Jeffrey Damman, James Eales, Ali G Gharavi, Vilmantas Giedraitis, Andrew C Heath, Eli Ipp, Krzysztof Kiryluk, Holly J Kramer, Michiaki Kubo, Anders Larsson, Cecilia M Lindgren, Yingchang Lu, Pamela A F Madden, Grant W Montgomery, George J Papanicolaou, Leslie J Raffel, Ralph L Sacco, Elena Sanchez, Holger Stark, Johan Sundstrom, Kent D Taylor, Anny H Xiang, Aleksandra Zivkovic, Lars Lind, Erik Ingelsson, Nicholas G Martin, John B Whitfield, Jianwen Cai, Cathy C Laurie, Yukinori Okada, Koichi Matsuda, Charles Kooperberg, Yii-Der Ida Chen, Tatjana Rundek, Stephen S Rich, Ruth J F Loos, Esteban J Parra, Miguel Cruz, Jerome I Rotter, Harold Snieder, Maciej Tomaszewski, Benjamin D Humphreys, Nora Franceschini
Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron...
January 3, 2019: Nature Communications
Felix J Boivin, Kai M Schmidt-Ott
Proper renal function relies on the tightly regulated development of nephrons and collecting ducts. This process, known as tubulogenesis, involves dynamic cellular and molecular changes that instruct cells to form highly organized tubes of epithelial cells which compartmentalize the renal interstitium and tubular lumen via assembly of a selective barrier. The integrity and diversity of the various renal epithelia is achieved via formation of intercellular protein complexes along the apical-basal axis of the epithelial cells...
December 15, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Jacques Teulon, Gabrielle Planelles, Francisco V Sepúlveda, Olga Andrini, Stéphane Lourdel, Marc Paulais
The many mechanisms governing NaCl absorption in the diverse parts of the renal tubule have been largely elucidated, although some of them, as neutral NaCl absorption across the cortical collecting duct or regulation through with-no-lysine (WNK) kinases have emerged only recently. Chloride channels, which are important players in these processes, at least in the distal nephron, are the focus of this review. Over the last 20-year period, experimental studies using molecular, electrophysiological, and physiological/functional approaches have deepened and renewed our views on chloride channels and their role in renal function...
December 13, 2018: Comprehensive Physiology
Hideharu Abe, Akiko Sakurai, Arisa Ochi
The glomerulus is a network of capillaries known as a tuft, located at the beginning of a nephron in the kidney. Here we describe a novel method for the induction of a macroscopically visible three-dimensional glomerulus-like sphere (GLS). This procedure did not require any additional cytokines and completed the formation of spheres within 24 h. After the formation was complete, GLS maintained a steady state for at least five days without proliferation and without a decrease in viability. Therefore, this procedure assists various assays for a prolong period of time...
December 3, 2018: Biochemical and Biophysical Research Communications
Ping Wang, Yidong Chen, Jun Yong, Yueli Cui, Rui Wang, Lu Wen, Jie Qiao, Fuchou Tang
Healthy renal function depends on normal nephrogenesis during embryonic development. However, a comprehensive gene expression profile of human fetal kidney development remains largely unexplored. Here, using a single-cell RNA-sequencing technique, we analyzed >3,000 human fetal renal cells spanning 4 months of development in utero. Unsupervised analysis identified two progenitor subtypes during cap mesenchyme development, suggesting a mechanism for sustaining their progenitor states. Furthermore, we identified critical transcriptional regulators and signaling pathways involved in the segmentation of nephron tubules...
September 25, 2018: Cell Reports
Fedor Kundert, Louise Platen, Takamasa Iwakura, Zhibo Zhao, Julian A Marschner, Hans-Joachim Anders
Acute kidney injury is a clinical syndrome that can be caused by numerous diseases including acute tubular necrosis (ATN). ATN evolves in several phases, all of which are accompanied by different immune mechanisms as an integral component of the disease process. In the early injury phase, regulated necrosis, damage-associated molecular patterns, danger sensing, and neutrophil-driven sterile inflammation enhance each other and contribute to the crescendo of necroinflammation and tissue injury. In the late injury phase, renal dysfunction becomes clinically apparent, and M1 macrophage-driven sterile inflammation contributes to ongoing necroinflammation and renal dysfunction...
September 2018: Kidney Research and Clinical Practice
Anneliis Ihermann-Hella, Tsuyoshi Hirashima, Jussi Kupari, Kristen Kurtzeborn, Hao Li, Hyuk Nam Kwon, Cristina Cebrian, Abdul Soofi, Arvydas Dapkunas, Ilkka Miinalainen, Gregory R Dressler, Michiyuki Matsuda, Satu Kuure
The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Förster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiating precursors exhibited sustained activity. Genetic experiments demonstrate that MAPK/ERK activity controls the thickness, coherence, and integrity of the nephron progenitor niche...
October 9, 2018: Stem Cell Reports
Chien-Ming Lin, Chih-Jen Cheng, Sung-Sen Yang, Min-Hua Tseng, Ming-Tso Yen, Chih-Chien Sung, Shih-Hua Lin
The Kelch-like 3 ( KLHL3) mutations contributed to the most common causative genes in patients with pseudohypoaldosteronism type II (PHAII); however, the molecular mechanisms of PHAII-causing mutations in BTB domain of KLHL3 in vivo have not been investigated. We generated and analyzed Klhl3 knock-in (KI) mice carrying a missense M131V mutation in the BTB domain (corresponding to human KLHL3 M78V mutation). Klhl3M131V/+ KI mice exhibited typical PHAII phenotype with an exaggerated diuretic response to hydrochlorothiazide...
August 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Lori L O'Brien
The filtering component of the kidney, the nephron, arises from a single progenitor population. These nephron progenitor cells (NPCs) both self-renew and differentiate throughout the course of kidney development ensuring sufficient nephron endowment. An appropriate balance of these processes must be struck as deficiencies in nephron numbers are associated with hypertension and kidney disease. This review will discuss the mechanisms and molecules supporting NPC maintenance and differentiation. A focus on recent work will highlight new molecular insights into NPC regulation and their dynamic behavior in both space and time...
July 30, 2018: Seminars in Cell & Developmental Biology
Silvia Ferrè, Peter Igarashi
Hepatocyte nuclear factor-1β (HNF-1β) is an essential transcription factor that regulates the development and function of epithelia in the kidney, liver, pancreas, and genitourinary tract. Humans who carry HNF1B mutations develop heterogeneous renal abnormalities, including multicystic dysplastic kidneys, glomerulocystic kidney disease, renal agenesis, renal hypoplasia, and renal interstitial fibrosis. In the embryonic kidney, HNF-1β is required for ureteric bud branching, initiation of nephrogenesis, and nephron segmentation...
July 1, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Lillie M A Barnett, Brian S Cummings
The kidney consists of numerous cell types organized into the nephron, which is the basic functional unit of the kidney. Any stimuli that induce loss of these cells can induce kidney damage and renal failure. The cause of renal failure can be intrinsic or extrinsic. Extrinsic causes include cardiovascular disease, obesity, diabetes, sepsis, and lung and liver failure. Intrinsic causes include glomerular nephritis, polycystic kidney disease, renal fibrosis, tubular cell death, and stones. The kidney plays a prominent role in mediating the toxicity of numerous drugs, environmental pollutants and natural substances...
August 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Oleg Palygin, Oleh Pochynyuk, Alexander Staruschenko
PURPOSE OF REVIEW: Multiple clinical and translational evidence support benefits of high potassium diet; however, there many uncertainties underlying the molecular and cellular mechanisms determining effects of dietary potassium. Kir4.1 and Kir5.1 proteins form a functional heteromer (Kir4.1/Kir5.1), which is the primary inwardly rectifying potassium channel on the basolateral membrane of both distal convoluted tubule (DCT) and the collecting duct principal cells. The purpose of this mini-review is to summarize latest advances in our understanding of the evolution, physiological relevance and mechanisms controlling these channels...
September 2018: Current Opinion in Nephrology and Hypertension
Tahagod Mohamed, Maria Luisa S Sequeira-Lopez
The kidney vasculature has a unique and complex architecture that is central for the kidney to exert its multiple and essential physiological functions with the ultimate goal of maintaining homeostasis. An appropriate development and coordinated assembly of the different vascular cell types and their association with the corresponding nephrons is crucial for the generation of a functioning kidney. In this review we provide an overview of the renal vascular anatomy, histology, and current knowledge of the embryological origin and molecular pathways involved in its development...
June 5, 2018: Seminars in Cell & Developmental Biology
Sung Yoon Lim, Yoon Sook Ko, Hee Young Lee, Ji Hyun Yang, Myung Gyu Kim, Sang Kyung Jo, Won Yong Cho
BACKGROUND: Recent observational studies have shown that in chronic kidney disease (CKD) patients, a significantly smaller percentage of patients with an episode of acute kidney injury (AKI) have full recovery of renal function compared to those without CKD. However, precise mechanisms involved in the incomplete repair after AKI with preexisting CKD have not been completely ascertained. Here, we assessed the impact of preexisting CKD on the severity and recovery of AKI in a mouse model of 5/6 nephrectomy...
2018: Nephron
Martin Höhne, Christian K Frese, Florian Grahammer, Claudia Dafinger, Giuliano Ciarimboli, Linus Butt, Julia Binz, Matthias J Hackl, Mahdieh Rahmatollahi, Martin Kann, Simon Schneider, Mehmet M Altintas, Bernhard Schermer, Thomas Reinheckel, Heike Göbel, Jochen Reiser, Tobias B Huber, Rafael Kramann, Tamina Seeger-Nukpezah, Max C Liebau, Bodo B Beck, Thomas Benzing, Andreas Beyer, Markus M Rinschen
In diseases of many parenchymatous organs, heterogeneous deterioration of individual functional units determines the clinical prognosis. However, the molecular characterization at the level of such individual subunits remains a technological challenge that needs to be addressed in order to better understand pathological mechanisms. Proteinuric glomerular kidney diseases are frequent and assorted diseases affecting a fraction of glomeruli and their draining tubules to variable extents, and for which no specific treatment exists...
June 2018: Kidney International
K Johanna R Hoyer, Sebastian Dittrich, Malte P Bartram, Markus M Rinschen
Renal diseases are driven by alterations in the entity of proteins within the kidney, at the level of single cells, nephron subunits (such as glomerulus and tubule), tissues and body fluids. Histologically, kidney diseases are extremely heterogeneous. Mass-spectrometry based proteomics provides a unique opportunity to interrogate heterogeneity and dynamics of various proteome layers within the kidney to better understand physiology and pathophysiology, and to translate signaling networks into therapies. Yet, the success of this endeavor will largely depend on improving proteomic data acquisition methods toward increased reproducibility...
March 6, 2018: Journal of Proteomics
Miriam Zacchia, Giovanna Capolongo, Luca Rinaldi, Giovambattista Capasso
The thick ascending limb (TAL) of Henle's loop is a crucial segment for many tasks of the nephron. Indeed, the TAL is not only a mainstay for reabsorption of sodium (Na+ ), potassium (K+ ), and divalent cations such as calcium (Ca2+ ) and magnesium (Mg2+ ) from the luminal fluid, but also has an important role in urine concentration, overall acid-base homeostasis, and ammonia cycle. Transcellular Na+ transport along the TAL is a prerequisite for Na+ , K+ , Ca2+ , Mg2+ homeostasis, and water reabsorption, the latter through its contribution in the generation of the cortico-medullar osmotic gradient...
2018: International Journal of Nephrology and Renovascular Disease
Nils O Lindström, Tracy Tran, Jinjin Guo, Elisabeth Rutledge, Riana K Parvez, Matthew E Thornton, Brendan Grubbs, Jill A McMahon, Andrew P McMahon
The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal-distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity...
March 2018: Journal of the American Society of Nephrology: JASN
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