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American Journal of Physiology. Renal Physiology

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https://www.readbyqxmd.com/read/29790392/interleukin-1-receptor-il-1r1-activation-exacerbates-toxin-induced-acute-kidney-injury
#1
Jamie R Privratsky, Jiandong Zhang, Xiaohan Lu, Nathan Rudemiller, Qingqing Wei, Yen-Rei Yu, Michael Dee Gunn, Steven D Crowley
Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Cisplatin is an effective chemotherapeutic agent whose administration is limited by nephrotoxicity. Therapies to prevent cisplatin-induced AKI are lacking. While tumor necrosis factor-α (TNF) plays a key role in the pathogenesis of cisplatin nephrotoxicity, the immune signaling pathways that trigger TNF generation in this context require elucidation. Sterile injury triggers the release and activation of both isoforms of interleukin(IL)-1, IL-1α and IL-1β, and stimulation of the interleukin-1 receptor (IL-1R1) by these ligands engages a pro-inflammatory signaling cascade that induces TNF induction...
May 23, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29790391/neutrophil-exocytosis-induces-podocyte-cytoskeletal-reorganization-and-proteinuria-in-experimental-glomerulonephritis
#2
Dawn J Caster, Erik A Korte, Min Tan, Michelle T Barati, Shweta Tandon, T Michael Creed, David J Salant, Jessica L Hata, Paul N Epstein, Hui Huang, David W Powell, Kenneth R McLeish
Acute glomerulonephritis is characterized by rapid glomerular neutrophil recruitment, proteinuria, and glomerular hypercellularity. The current study tested the hypothesis that release of neutrophil granule contents plays a role in both loss of filtration barrier leading to proteinuria and the increase in glomerular cells. Inhibition of neutrophil exocytosis with a peptide inhibitor prevented proteinuria and attenuated podocyte and endothelial cell injury, but had no effect on glomerular hypercellularity in an experimental acute glomerulonephritis model in mice...
May 23, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29790390/collecting-duct-principal-but-not-intercalated-cell-prorenin-receptor-regulates-renal-sodium-and-water-excretion
#3
Nirupama Ramkumar, Deborah Stuart, Elena Mironova, Nikita Abraham, Yang Gao, Shuping Wang, Jayalakshmi Lakshmipathi, James D Stockand, Donald E Kohan
The collecting duct is the predominant nephron site of prorenin and prorenin receptor (PRR) expression. We previously demonstrated that the collecting duct PRR regulates epithelial Na+ channel (ENaC) activity and water transport; however, which cell type is involved remains unclear. Herein, we examined the effects of principal cell (PC) or intercalated cell (IC) PRR deletion on renal Na+ and water handling. PC or IC PRR KO mice were obtained by crossing floxed PRR mice with mice harboring Cre recombinase under the control of the AQP2 or B-1 subunit of the H+ ATPase promoters, respectively...
May 23, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29790389/unmasking-a-sustained-negative-effect-of-sglt2-inhibition-on-body-fluid-volume-in-the-rat
#4
Takahiro Masuda, Yuko Watanabe, Keiko Fukuda, Minami Watanabe, Akira Onishi, Ken Ohara, Toshimi Imai, Hermann Koepsell, Shigeaki Muto, Volker Vallon, Daisuke Nagata
The chronic intrinsic diuretic and natriuretic tone of sodium-glucose cotransporter 2 (SGLT2) inhibitors is incompletely understood, because their effect on body fluid volume (BFV) has not been fully evaluated and because they often increase food and fluid intake at the same time. Here we first compared the effect of the SGLT2 inhibitor ipragliflozin (Ipra, 0.01% in diet for 8 weeks) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a non-obese type 2 diabetic model, and non-diabetic Sprague-Dawley rats...
May 23, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29790388/graft-function-assessment-in-mouse-models-of-single-and-dual-kidney-transplantation
#5
Lei Wang, Ximing Wang, Shan Jiang, Jin Wei, Jacentha Buggs, Liying Fu, Jie Zhang, Ruisheng Liu
Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild type recipients or vise verse. Dual kidney transplantation (DKT) provides a more physiological environment for recipients than single kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT...
May 23, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29767559/g-protein-pathway-suppressor-2-gps2-enhanced-the-renal-large-conductance-ca2-activated-potassium-channel-expression-via-inhibiting-erk-1-2-signaling-pathway
#6
Zhizhi Zhuang, Jia Xiao, Xinxin Chen, Xiaohan Hu, Ruidian Li, Shan Chen, Xiuyan Feng, Saier Shen, He-Ping Ma, Jieqiu Zhuang, Hui Cai
G-protein pathway suppressor 2 (GPS2) is a multifunctional protein and transcriptional regulation factor that is involved in the G-protein mitogen-activated protein kinase (MAPK) signaling pathway. It has been shown that the MAPK signaling pathway plays an important role in the regulation of renal large conductance Ca2+ activated potassium (BK) channels. In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. In HEK BK stably-expressing cells transfected with either GPS2 or its pCMV vector control, a single cell recording showed that GPS2 significantly increased BK channel activity (NPo), increasing BK open probability (Po) and channel number (N) compared to the control...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29767558/molecular-basis-of-the-counteraction-by-calcium-channel-blockers-of-cyclosporine-nephrotoxicity
#7
Safaa Hicham Hammoud, Sahar Alkhansa, Neamah Mahjoub, Amal Galal Omar, Mahmoud M El-Mas, Assaad A Eid
Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine (CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorate renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats (n=6/group) were used and received one of the following treatments for 7 consecutive days: vehicle (cremophor EL, i...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29767557/polycystin-1-dysfunction-impairs-electrolyte-and-water-handling-in-a-renal-pre-cystic-mouse-model-for-adpkd
#8
Eric H J Verschuren, Sami G Mohammed, Wouter N Leonhard, Caro Overmars-Bos, Kimberly A M Veraar, Joost G J Hoenderop, René J M Bindels, Dorien J M Peters, Francisco J Arjona
The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp-Pkd1-/-) mice manifesting a pre-cystic phenotype...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29767556/hydronephrosis-is-associated-with-elevated-plasmin-in-urine-in-pediatric-patients-and-rats-and-changes-in-ncc-and-%C3%AE-enac-abundance-in-rat-kidney
#9
Rikke Zachar, Ammar Al-Mashhadi, Henrik Dimke, Per Svenningsen, Boye L Jensen, Mattias Carlström
Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na+ transporters; and iii) the injured UPJO kidney allows aberrant filtration of plasminogen leading to proteolytic activation of the epithelial sodium channel gamma subunit (γ-ENaC)...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29767555/protective-effect-of-the-bet-protein-inhibitor-jq1-in-cisplatin-induced-nephrotoxicity
#10
Liping Sun, Jing Liu, Yanggang Yuan, Xinzhou Zhang, Zheng Dong
As a potent chemotherapy drug, cisplatin is also notorious for its side effects including nephrotoxicity in kidneys, presenting a pressing need to identify renoprotective agents. Cisplatin nephrotoxicity involves epigenetic regulations, including changes in histone acetylation. Bromodomain and extra-terminal (BET) proteins are "readers" of the epigenetic code of histone acetylation. Here, we investigated the potential renoprotective effects of JQ1, a small molecule inhibitor of BET proteins. We show that JQ1 significantly ameliorated cisplatin-induced nephrotoxicity in mice as indicated by the measurements of kidney function, histopathology, and renal tubular apoptosis...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29741098/monophosphoryl-lipid-a-prevents-impairment-of-medullary-thick-ascending-limb-hco-3-absorption-and-improves-plasma-hco-3-concentration-in-septic-mice
#11
Bruns A Watts, Thampi George, Edward R Sherwood, David W Good
Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs HCO3 - absorption in the MTAL by: 1) decreasing the intrinsic HCO3 - absorptive capacity, and 2) enhancing inhibition of HCO3 - absorption by LPS through upregulation of TLR4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis...
May 9, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29717938/comparison-of-folate-conjugated-rapamycin-versus-unconjugated-rapamycin-in-an-orthologous-mouse-model-of-polycystic-kidney-disease
#12
Kevin R Kipp, Samantha L Kruger, Margaret F Schimmel, Nikki Parker, Jonathan M Shillingford, Christopher P Leamon, Thomas Weimbs
Autosomal-dominant polycystic kidney disease (ADPKD) is a very common genetic disease leading to renal failure. Numerous aberrantly regulated signaling pathways have been identified as promising molecular drug targets for ADPKD therapy. In rodent models, many small-molecule drugs against such targets have proven effective in reducing renal cyst growth. For example, mTOR inhibition with rapamycin greatly ameliorates renal cystic disease in several rodent models. However, clinical trials with mTOR inhibitors were disappointing largely due to the intolerable extra-renal side effects during long-term treatment with these drugs...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29717937/deletion-or-pharmacological-blockade-of-toll-like-receptor-4-tlr4-confers-protection-against-cyclophosphamide-induced-mouse-cystitis
#13
Mariana G de Oliveira, Fabiola Zakia Mónica, Fabiano B Calmasini, Eduardo C Alexandre, Edith B G Tavares, Antonio G Soares, Soraia K P Costa, Edson Antunes
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. We investigate the role of toll-like receptor (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)-induced mouse cystitis. Males C57BL/6 (wild-type, WT) and/or TLR4 knockout (TLR4-/-) were treated with an injection of CYP (300 mg/kg, 24 h) or saline (10 ml/kg). The pharmacological blockade of the TLR4 by resatorvid (10 mg/kg) was also performed 1 h prior CYP-injection in WT mice...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29717936/different-effects-of-global-osteopontin-and-macrophage-osteopontin-in-glomerular-injury
#14
Jessica Trostel, Luan D Truong, Carlos A Roncal-Jimenez, Makoto Miyazaki, Shinobu Miyazaki-Anzai, Masanari Kuwabara, Rachel H McMahan, Ana Andres-Hernando, Yuka Sato, Thomas Jensen, Miguel A Lanaspa, Richard J Johnson, Gabriela E Garcia
Osteopontin (OPN) is a pro-and ant-inflammatory molecule that simultaneously attenuates oxidative stress. Both inflammation and oxidative stress play a role in the pathogenesis of glomerulonephritis and in the progression of kidney injury. Importantly, OPN is highly induced in nephritic kidney. To further characterize the role of OPN in kidney injury we used OPN-/- mice in anti-glomerular basement membrane reactive serum-induced immune nephritis (NTS), an inflammatory and progressive model of kidney disease...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29717935/expression-of-soluble-epoxide-hydrolase-in-renal-tubular-epithelial-cells-regulates-macrophage-infiltration-and-polarization-in-iga-nephropathy
#15
Qian Wang, Yan Liang, Yingjin Qiao, Xiangya Zhao, Yi Yang, Shengnan Yang, Bing Li, Qianru Zhao, Ling Dong, Songxia Quan, Rui Tian, Zhangsuo Liu
Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in kidney remains unknown...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29693450/the-impact-of-preserved-klotho-gene-expression-on-anti-oxidative-stress-activity-in-healthy-kidney
#16
Takaaki Kimura, Kazuhiro Shiizaki, Hiroshi Kurosu, Tetsu Akimoto, Takahiro Shinzato, Toshihiro Shimizu, Akira Kurosawa, Taro Kubo, Koji Nanmoku, Makoto Kuro-O, Takashi Yagisawa
Klotho, which was originally identified as an anti-aging gene, forms a complex with fibroblast growth factor 23 (FGF23) receptor in kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho including anti-aging effects such as protection from various cellular stress have been shown, however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and anti-oxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied...
April 25, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29693449/a-translational-model-of-chronic-kidney-disease-in-swine
#17
Alejandro R Chade, Maxx L Williams, Jason E Engel, Erika Guise, Taylor W Harvey
Animal models of chronic kidney disease (CKD) are critical for understanding its pathophysiology and for therapeutic development. The cardiovascular and renal anatomy and physiology of the pig are virtually identical to humans. This study aimed to develop a novel translational model of CKD that mimics the pathological features of CKD in humans. CKD was induced in 7 domestic pigs by bilateral renal artery stenosis and diet-induced dyslipidemia. Animals were observed for a total of 14 weeks. Renal hemodynamics and function were quantified in vivo using multi-detector CT after 6, 10, and 14 weeks of CKD...
April 25, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29693448/three-dimensional-in-vitro-models-answer-the-right-questions-in-adpkd-cystogenesis
#18
Eryn E Dixon, Owen M Woodward
Novel technologies, new understanding of the basement membrane composition, and better comprehension of the embryonic development of the mammalian kidney have led to explosive growth in the use of three dimensional (3D) in vitro models to study a range of human disease pathologies(6, 35). The development of these effective model systems represents a new tool to study the progressive cystogenesis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a prevalent and complex monogenetic disease, characterized by the pathological formation of fluid fill cysts in renal tissue(17, 40)...
April 25, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29693447/chronic-kidney-disease-uremic-milieu-and-its-effects-on-gut-bacterial-microbiota-dysbiosis
#19
Lee D Chaves, Daniel I McSkimming, Mark A Bryniarski, Amanda M Honan, Sham Abyad, Shruthi A Thomas, Steven Wells, Michael J Buck, Yijun Sun, Robert J Genco, Richard J Quigg, Rabi Yacoub
Several lines of evidence suggest that gut bacterial microbiota is altered in patients with chronic kidney disease (CKD), though the mechanism of which this dysbiosis takes place is not well understood. Recent studies delineated changes in gut microbiota in both CKD patients and experimental animal models using microarray chips. We present 16S ribosomal RNA gene sequencing of both stool pellets and small bowel contents of C57Bl/6J mice that underwent a remnant kidney model, and establish that changes in microbiota take place in the early gastrointestinal track...
April 25, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29672130/nadph-oxidase-4-derived-superoxide-mediates-flow-stimulated-nkcc2-activity-in-thick-ascending-limbs
#20
Fara Saez, Nancy J Hong, Jeffrey L Garvin
Luminal flow augments sodium reabsorption in the thick ascending limb more than can be explained by increased ion delivery. This segment reabsorbs 30% of the filtered load of sodium, playing a key role in its homeostasis. Whether flow elevations enhance Na/K/2Cl cotransporter (NKCC2) activity and the second messenger involved are unknown. We hypothesized that raising luminal flow augments NKCC2 activity by enhancing O2 - production by NADPH oxidase 4 (NOX4). NKCC2 activity was measured in thick ascending limbs perfused at either 5 or 20 nl/min with and without inhibitors of O2 - production...
April 19, 2018: American Journal of Physiology. Renal Physiology
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