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American Journal of Physiology. Renal Physiology

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https://www.readbyqxmd.com/read/27903492/angiotensinogen-import-in-isolated-proximal-tubules-evidence-for-mitochondrial-trafficking-and-uptake
#1
Bryan A Wilson, Nildris Cruz-Diaz, Yixin Su, James C Rose, TanYa M Gwathmey, Mark C Chappell
The renal proximal tubules are a key functional component of the kidney and express the angiotensin precursor angiotensinogen; however, it is unclear the extent that tubular angiotensinogen reflects local synthesis or internalization. Therefore, the current study established the extent that angiotensinogen is internalized by proximal tubules and the intracellular distribution. Proximal tubules were isolated from the kidney cortex of male sheep by enzymatic digestion and a discontinuous Percoll gradient. Tubules were incubated with radiolabeled 125I-angiotensinogen for 2 hrs at 37°C in serum/phenol-free DMEM/F12 media...
November 30, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27881397/a-simple-method-to-ensure-homogeneous-drug-distribution-during-intrarenal-infusion
#2
Dmitry D Postnov, Max Salomonsson, Charlotte M Sorensen, Olga V Sosnovtseva
Intrarenal drug infusion plays an important role in renal experimental research. Laminar flow of the blood can cause streaming and inhomogeneous intrarenal distribution of infused drugs. We suggest a simple method to achieve a homogeneous intravascular distribution of drugs infused into the renal artery of anesthetized rats. The method employs a multiple sidehole catheter inserted into the renal artery, which enables an efficient drug mixing with the arterial blood. To verify the efficiency of this method we use laser speckle imaging and renal artery flowmetry...
November 23, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27881396/involvement-of-infiltrating-macrophage-derived-activin-a-in-the-progression-of-renal-damage-in-mrl-lpr-mice
#3
Anastasie Thilela Kadiombo, Akito Maeshima, Ken Kayakabe, Hidekazu Ikeuchi, Toru Sakairi, Yoriaki Kaneko, Keiju Hiromura, Yoshihisa Nojima
Lupus nephritis is a life-threatening complication of systemic lupus erythematosus (SLE). Various growth factors, cytokines, and chemokines are implicated in the development of SLE. However, the pathophysiological processes involved in the development of lupus nephritis still remain unclear. In this study, we examined the involvement of activin A, a member of TGF-β superfamily, in the progression of renal damage in lupus-prone MRL-lpr mice. Activin A was was not expressed in the kidneys of normal C57BL/6 mice but was detectable in perivascular infiltrating CD68-positive cells in the kidneys of MRL-lpr mice...
November 23, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27852611/the-critical-role-of-kr%C3%A3-ppel-like-factors-in-kidney-disease
#4
Sandeep K Mallipattu, Chelsea C Estrada, John Cijiang He
Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have been identified, and several have been well characterized in the kidney. Although they may share some overlap in their downstream targets, their structure and function remain distinct...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27852610/vascular-endothelium-in-diabetes
#5
Michael S Goligorsky
Three decades ago a revolutionary idea ascribing to dysfunctional endothelia some manifestations of diabetes was born, the Steno hypothesis. Here I briefly outline the accomplishments made in the past 15 years to buttress this hypothesis. Those include development of novel technological platforms to examine microcirculatory beds, deeper understanding of patterns of microvascular derangement in diabetes, pathophysiology of nitric oxide synthesis and availability, nitrosative and oxidative stress in diabetes, premature senescence of endothelial cells and the role of sirtuin 1 and lysosomal dysfunction in this process, state of endothelial glycocalyx and endothelial progenitor cells in diabetes...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27852609/il-17-mediates-neutrophil-infiltration-and-renal-fibrosis-following-recovery-from-ischemia-reperfusion-compensatory-role-of-natural-killer-cells-in-athymic-rats
#6
Purvi Mehrotra, Jason A Collett, Seth McKinney, Jackson Stevens, Carlie M Ivancic, David P Basile
T cells have been implicated in the pathogenesis of AKI as well as its progression to CKD. Previous studies suggest that Th17 cells participates during the AKI to CKD transition and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal I/R was performed on T cell deficient athymic rats (Foxn1rnu-/rnu-) and control euthymic rats (Foxn1rnu-/+) and CKD progression was hastened by unilateral nephrectomy at Day 33 and subsequent exposure to 4...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27852608/dba2j-db-db-mice-are-susceptible-to-early-albuminuria-and-glomerulosclerosis-that-correlates-with-systemic-insulin-resistance
#7
Mette Viberg Østergaard, Vanda Pinto, Kirsty Stevenson, Jesper Worm, Lisbeth N Fink, Richard John Mark Coward
Diabetic nephropathy (DN) is the leading cause of kidney failure in the world. To understand important mechanisms underlying this condition, and to develop new therapies, good animal models are required. In mouse models of type-1 diabetes, the DBA/2J strain has been shown to be more susceptible to develop kidney disease than other common strains. We hypothesized this would also be the case in type-2 diabetes. We studied db/db and wt DBA/2J mice and compared these with the db/db BLKS/J mouse, which is currently the most widely used type-2 DN model...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27852607/ion-transport-in-the-zebrafish-kidney-from-a-human-disease-angle-possibilities-considerations-and-future-perspectives
#8
Simone Kersten, Francisco J Arjona
Unique experimental advantages, such as its embryonic/larval transparency, high-throughput nature and ease of genetic modification, underpin the rapid emergence of the zebrafish (Danio rerio) as a preeminent model in biomedical research. Particularly in the field of nephrology, the zebrafish provides a promising model for studying the physiological implications of human solute transport processes along consecutive nephron segments. However, while the zebrafish might be considered a valuable model for numerous renal ion transport diseases and functional studies of many channels and transporters, not all human renal electrolyte transport mechanisms and human diseases can be modeled in the zebrafish...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27806944/the-mechanosensitive-bk%C3%AE-%C3%AE-1-channel-localizes-to-cilia-of-principal-cells-in-rabbit-cortical-collecting-duct-ccd
#9
Rolando Carrisoza-Gaytán, Lijun Wang, Carlos M N Schreck, Thomas R Kleyman, Wen-Hui Wang, Lisa M Satlin
Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca(2+)- and/or stretch-dependent flow-induced K(+) secretion (FIKS) and contributes to K(+) adaptation in response to dietary K(+) loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K(+) secretory processes. In support for a role for ICs in FIKS is the higher density of immunoreactive apical BKα (pore forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα expression in response to a high K(+) diet...
November 2, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784697/outside-the-mainstream-novel-collecting-duct-proteins-regulating-water-balance
#10
Shamma S Rahman, Erika I Boesen
Body water balance is critical to survival and therefore very tightly regulated by the hypothalamus and kidney. A key mechanism involved in this process, the arginine vasopressin (AVP)-mediated phosphorylation and apical membrane insertion of aquaporin 2 (AQP2) in the collecting duct, has been extensively studied; however, with the increased availability of conditional knockout animals, several novel collecting duct proteins have recently been implicated in water homeostasis. In this Mini-Review, we briefly discuss these novel proteins and their roles in the regulation of water homeostasis...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784696/serine-threonine-phosphatases-and-aquaporin-2-regulation-in-renal-collecting-duct
#11
Sophia LeMaire, Viswanathan Raghuram, Cameron R Grady, Christina M Pickering, Chung-Lin Chou, Ezigbobiara N Umejiego, Mark A Knepper
Phosphorylation of the aquaporin-2 (AQP2) water channel at four COOH-terminal serines plays a central role in the regulation of water permeability of the renal collecting duct. The level of phosphorylation at these sites is determined by a balance between phosphorylation by protein kinases and dephosphorylation by phosphatases. The phosphatases that dephosphorylate AQP2 have not been identified. Here, we use large-scale data integration techniques to identify serine-threonine phosphatases likely to interact with AQP2 in renal collecting duct principal cells...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784695/impaired-urinary-osteopontin-excretion-in-npt2a-mice
#12
Daniel Caballero, Yuwen Li, Julian Ponsetto, Chuanlong Zhu, Clemens Bergwitz
Mutations in the renal sodium-dependent phosphate co-transporters NPT2a and NPT2c have been reported in patients with renal stone disease and nephrocalcinosis. Oral phosphate supplementation is currently thought to reduce risk by reversing the hypercalciuria, but the exact mechanism remains unclear and the relative contribution of modifiers of mineralization such as osteopontin (Opn) to the formation of renal mineral deposits in renal phosphate wasting disorders has not been studied. We observed a marked decrease of renal gene expression and urinary excretion of Opn in Npt2a-/- mice, a mouse model of these disorders, at baseline...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784694/deficiency-of-mpges-1-exacerbates-renal-fibrosis-and-inflammation-in-mice-with-unilateral-ureteral-obstruction
#13
Renfei Luo, Yutaka Kakizoe, Feifei Wang, Xiang Fan, Shan Hu, Tianxin Yang, Weidong Wang, Chunling Li
Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 to prostaglandin E2 (PGE2), plays an important role in a variety of inflammatory diseases. We investigated the contribution of mPGES-1 to renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) for 7 days using wild type (WT) and mPGES-1 knockout (KO) mice. UUO induced increased mRNA and protein expression of mPGES-1 and cyclooxygenase-2 in WT mice. UUO was associated with increased renal PGE2 content and upregulated PGE2 receptor (EP) 4 expression in obstructed kidneys of both WT and KO mice; EP4 expression levels were higher in KO mice with UUO than that in WT mice...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784693/physiological-roles-of-claudins-in-kidney-tubule-paracellular-transport
#14
Shigeaki Muto
The paracellular pathways in renal tubular epithelia such as the proximal tubules, which reabsorb the largest fraction of filtered solutes and water and are leaky epithelia, are important routes for transepithelial transport of solutes and water. Movement occurs passively via an extracellular route through the tight junction between cells. The characteristics of paracellular transport vary among different nephron segments with leaky or tighter epithelia. Claudins expressed at tight junctions form pores and barriers for paracellular transport...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784692/a-kidney-selective-biopolymer-for-targeted-drug-delivery
#15
Gene L Bidwell, Fakhri Mahdi, Qingmei Shao, Omar C Logue, Jamarius P Waller, Caleb Reese, Alejandro R Chade
Improving drug delivery to the kidney using renal-targeted therapeutics is a promising but under-developed area. We aimed to develop a kidney-targeting construct for renal-specific drug delivery. Elastin-like polypeptides (ELPs) are non-immunogenic protein-based carriers that can stabilize attached small molecule and peptide therapeutics. We modified ELP at its N-terminus with a cyclic, seven amino acid kidney-targeting peptide (KTP) and at its C-terminus with a cysteine residue for tracer conjugation. Comparative in vivo pharmacokinetics and biodistribution in rat and swine models and in vitro cell binding studies using human renal cells were performed...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784691/crucial-roles-of-nitric-oxide-synthases-in-%C3%AE-adrenoceptor-mediated-bladder-relaxation-in-mice
#16
Yohei Satake, Kimio Satoh, Masamichi Nogi, Junichi Omura, Shigeo Godo, Satoshi Miyata, Hiroki Saito, Shuhei Tanaka, Yosuke Ikumi, Shinichi Yamashita, Yasuhiro Kaiho, Masato Tsutsui, Yoichi Arai, Hiroaki Shimokawa
The specific roles of NO synthases (NOSs) in bladder smooth muscle remain to be elucidated. We examined the roles of NOSs in β-adrenoceptor (AR)-mediated bladder relaxation. Male mice (C57BL6) deficient of neuronal NOS (nNOS-KO), endothelial NOS (eNOS-KO), neuronal/endothelial NOS (n/eNOS-KO), neuronal/endothelial/inducible NOS (n/e/iNOS-KO) and their controls (wild-type, WT) were used. Immunohistochemical analysis was performed in the bladder. Then, the responses to relaxing agents and the effects of several inhibitors on the relaxing responses were examined in bladder strips precontracted with carbachol...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27760773/stop-that-podocyte
#17
Vineet Gupta, Jochen Reiser
n/a.
October 19, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27760772/downregulation-of-kidney-expression-of-protective-factors-by-renal-and-systemic-inflammation-role-of-transcription-factors-and-epigenetic-mechanisms
#18
Olga Ruiz-Andres, Maria Dolores Sanchez-Niño, Juan Antonio Moreno, Marta Ruiz-Ortega, Adrian Mario Ramos, Ana Belén Sanz, Alberto Ortiz
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR)...
October 19, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27760771/molecular-mechanisms-regulating-aquaporin-2-in-kidney-collecting-duct
#19
Hyun Jun Jung, Tae-Hwan Kwon
Kidney collecting duct is an important renal tubular segment for regulation of body water homeostasis and urine concentration. Water reabsorption in the collecting duct principal cells is controlled by vasopressin, a peptide hormone which induces the osmotic water transport across the collecting duct epithelia through regulation of water channel proteins aquaporin-2 (AQP2) and aquaporin-3 (AQP3). In particular, vasopressin induces both intracellular translocation of AQP2-bearing vesicles to the apical plasma membrane and transcription of Aqp2 gene to increase AQP2 protein abundance...
October 19, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27760770/inflammation-drives-renal-scarring-in-experimental-pyelonephritis
#20
Birong Li, Babitha Haridas, Ashley R Jackson, Hanna Cortado, Nicholas Mayne, Rebecca Kohnken, Brad Bolon, Kirk M McHugh, Andrew L Schwaderer, John D Spencer, Christina B Ching, David S Hains, Sheryl S Justice, Santiago Partida-Sanchez, Brian Becknell
Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis...
October 19, 2016: American Journal of Physiology. Renal Physiology
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