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https://www.readbyqxmd.com/read/27920796/neutrophil-gelatinase-associated-lipocalin-fibroblast-growth-factor-23-and-soluble-klotho-in-long-term-kidney-donors
#1
Inga Strand Thorsen, Inger Hjørdis Bleskestad, Grete Jonsson, Øyvind Skadberg, Lasse Gunnar Gøransson
BACKGROUND: The best treatment for end-stage renal disease (ESRD) is kidney transplantation. Twenty-seven percent of transplantations in Norway are from living donors. Recent studies have shown an increased risk of ESRD and increased mortality in donors. The aim of this study was to determine if the levels of the new biomarkers neutrophil gelatinase-associated lipocalin (NGAL), soluble Klotho (sKlotho), and fibroblast growth factor 23 (FGF23) are changed in kidney donors with normal kidney function defined as an estimated glomerular filtration rate (eGFR) >60 ml/min/1...
September 2016: Nephron Extra
https://www.readbyqxmd.com/read/27916483/serum-klotho-protein-levels-and-their-correlations-with-the-progression-of-type-2-diabetes-mellitus
#2
Fang Nie, Dongming Wu, Hongfei Du, Xianggui Yang, Min Yang, Xueli Pang, Ying Xu
AIM: To investigate the associations of serum α-Klotho and β-Klotho levels with type 2 diabetes mellitus (T2DM) progression. METHODS: We evaluated 106 healthy controls and 261 cases of T2DM with or without diabetic complications (range: 45-84years). Serum α-Klotho and β-Klotho levels were analyzed using enzyme-linked immunosorbent assays. RESULTS: Compared to the healthy controls, α-Klotho and β-Klotho levels were significantly lower among patients with T2DM and with or without diabetic complications (P<0...
November 12, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27914707/adiponectin-alters-renal-calcium-and-phosphate-excretion-through-regulation-of-klotho-expression
#3
Joseph M Rutkowski, Johanne Pastor, Kai Sun, Sun K Park, I Alexandru Bobulescu, Christopher T Chen, Orson W Moe, Philipp E Scherer
The kidney controls systemic calcium and phosphate levels and disturbances of its control mechanisms can lead to a variety of diseases. The insulin-sensitizing adipokine adiponectin is renoprotective and accelerates functional recovery following renal injury. However, unlike other adipokines, adiponectin is reduced in obesity. High adiponectin levels are also correlated with bone loss, suggestive of an additional action in mineral metabolism. Using knockout, wild-type, and adiponectin-overexpressing transgenic mice, we sought to identify the mechanistic basis for adiponectin's ability to regulate calcium and phosphate balance at the level of the kidney...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27911795/klb-is-associated-with-alcohol-drinking-and-its-gene-product-%C3%AE-klotho-is-necessary-for-fgf21-regulation-of-alcohol-preference
#4
Gunter Schumann, Chunyu Liu, Paul O'Reilly, He Gao, Parkyong Song, Bing Xu, Barbara Ruggeri, Najaf Amin, Tianye Jia, Sarah Preis, Marcelo Segura Lepe, Shizuo Akira, Caterina Barbieri, Sebastian Baumeister, Stephane Cauchi, Toni-Kim Clarke, Stefan Enroth, Krista Fischer, Jenni Hällfors, Sarah E Harris, Saskia Hieber, Edith Hofer, Jouke-Jan Hottenga, Åsa Johansson, Peter K Joshi, Niina Kaartinen, Jaana Laitinen, Rozenn Lemaitre, Anu Loukola, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Ani Manichaikul, Hamdi Mbarek, Yuri Milaneschi, Alireza Moayyeri, Kenneth Mukamal, Christopher Nelson, Jennifer Nettleton, Eemil Partinen, Rajesh Rawal, Antonietta Robino, Lynda Rose, Cinzia Sala, Takashi Satoh, Reinhold Schmidt, Katharina Schraut, Robert Scott, Albert Vernon Smith, John M Starr, Alexander Teumer, Stella Trompet, André G Uitterlinden, Cristina Venturini, Anne-Claire Vergnaud, Niek Verweij, Veronique Vitart, Dragana Vuckovic, Juho Wedenoja, Loic Yengo, Bing Yu, Weihua Zhang, Jing Hua Zhao, Dorret I Boomsma, John Chambers, Daniel I Chasman, Toniolo Daniela, Eco de Geus, Ian Deary, Johan G Eriksson, Tõnu Esko, Volker Eulenburg, Oscar H Franco, Philippe Froguel, Christian Gieger, Hans J Grabe, Vilmundur Gudnason, Ulf Gyllensten, Tamara B Harris, Anna-Liisa Hartikainen, Andrew C Heath, Lynne Hocking, Albert Hofman, Cornelia Huth, Marjo-Riitta Jarvelin, J Wouter Jukema, Jaakko Kaprio, Jaspal S Kooner, Zoltan Kutalik, Jari Lahti, Claudia Langenberg, Terho Lehtimäki, Yongmei Liu, Pamela A F Madden, Nicholas Martin, Alanna Morrison, Brenda Penninx, Nicola Pirastu, Bruce Psaty, Olli Raitakari, Paul Ridker, Richard Rose, Jerome I Rotter, Nilesh J Samani, Helena Schmidt, Tim D Spector, David Stott, David Strachan, Ioanna Tzoulaki, Pim van der Harst, Cornelia M van Duijn, Pedro Marques-Vidal, Peter Vollenweider, Nicholas J Wareham, John B Whitfield, James Wilson, Bruce Wolffenbuttel, Georgy Bakalkin, Evangelos Evangelou, Yun Liu, Kenneth M Rice, Sylvane Desrivières, Steven A Kliewer, David J Mangelsdorf, Christian P Müller, Daniel Levy, Paul Elliott
Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10(-12)). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910102/association-of-serum-klotho-with-loss-of-bone-mineral-density-and-fracture-risk-in-older-adults
#5
Didier Chalhoub, Elisa Marques, Osorio Meirelles, Richard D Semba, Luigi Ferrucci, Suzanne Satterfield, Michael Nevitt, Jane A Cauley, Tamara Harris
OBJECTIVES: Klotho deficiency has been previously linked to aging-like phenotypes such as osteoporosis, cognitive impairment, and sarcopenia. Low serum klotho was shown to be related to grip strength and disability. Nonetheless, no previous study has explored the association between serum klotho and fractures. The purpose of this report is to examine the relationship of serum klotho with bone mineral density (BMD) loss and fractures in older adults. DESIGN: The Health, Aging, and Body Composition (Health ABC) Study is a longitudinal cohort study of 3,075 community-dwelling older adults...
December 2, 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27903993/effects-of-angiotensin-ii-receptor-blockade-on-soluble-klotho-and-oxidative-stress-in-calcineurin-inhibitor-nephrotoxicity-in-rats
#6
Sina Raeisi, Amir Ghorbanihaghjo, Hassan Argani, Siavoush Dastmalchi, Babollah Ghasemi, Teimour Ghazizadeh, Nadereh Rashtchizadeh, Mahboob Nemati, Mehran Mesgari Abbasi, Nasrin Bargahi, Ali Mota, Amir Mansour Vatankhah
INTRODUCTION: Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress...
November 2016: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/27890549/novel-functions-of-circulating-klotho
#7
REVIEW
Julia M Hum, Linda O'Bryan, Rosamund C Smith, Kenneth E White
A significant portion of the key biological functions of αKlotho (αKL) and its cognate ligand Fibroblast growth factor-23 (FGF23) have been revealed through the study of rare diseases of mineral metabolism. These findings have far reaching implications for common disorders such as chronic kidney disease-mineral bone disorder (CKD-MBD). αKL's predominant effect on mineral homeostasis is through its actions in the kidney as a co-receptor for FGF23, however emerging data has shed light on its capacity to act as a circulating factor through the cleavage of the transmembrane form of αKL ('mKL') to produce 'cleaved KL' or 'cKL'...
November 23, 2016: Bone
https://www.readbyqxmd.com/read/27885332/2-3-5-4-tetrahydroxystilbene-2-o-%C3%AE-d-glucoside-promotes-expression-of-the-longevity-gene-klotho
#8
Shuang Ling, Ju Duan, Rongzhen Ni, Jin-Wen Xu
The longevity gene klotho has numerous physiological functions, such as regulating calcium and phosphorus levels, delaying senescence, improving cognition, reducing oxidative stress, and protecting vascular endothelial cells. This study tested whether 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a small molecule with antiaging effects, regulates the expression and physiological effects of klotho. Our results showed that THSG dose-dependently increased the luciferase reporter activity of the klotho gene, reversed the decrease in mRNA and protein expression of klotho which was induced by angiotensin II in NRK-52E renal tubular epithelial cells, and increased klotho mRNA expression in the cerebral cortex, hippocampus, testis, and kidney medulla of spontaneously hypertensive rats...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27882180/concentrations-of-fetuin-a-osteoprotegerin-and-%C3%AE-klotho-in-patients-with-alcoholic-liver-cirrhosis
#9
Andrzej Prystupa, Anna Dąbrowska, Jarosław Jerzy Sak, Jerzy Tarach, Anna Toruń-Jurkowska, Patrycja Lachowska-Kotowska, Grzegorz Dzida
The aim of the present study was to evaluate the concentrations of fetuin-A, osteoprotegerin (OPG) and α-Klotho protein in patients with alcoholic cirrhosis at different stages of the disease, and to demonstrate that fetuin-A, osteoprotegin and α-Klotho may be used as markers of the severity of cirrhosis. A total of 54 patients with alcoholic liver cirrhosis treated in various hospitals in the Lublin region of Poland were randomly enrolled. The control group consisted of 18 healthy individuals without liver disease, who did not drink alcohol...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881156/klotho-sensitive-regulation-of-dendritic-cell-functions-by-vitamin-e
#10
Nguyen Thi Xuan, Phi Thi Thu Trang, Nguyen Van Phong, Nguyen Linh Toan, Do Minh Trung, Nguyen Duy Bac, Viet Linh Nguyen, Nguyen Huy Hoang, Nong Van Hai
BACKGROUND: Dendritic cells (DCs) are the most potent professional antigen-presenting cells for naive T cells to link innate and acquired immunity. Klotho, an anti-aging protein, participates in the regulation of Ca(2+) dependent migration in DCs. Vitamin E (VitE) is an essential antioxidant to protect cells from damage and elicits its inhibitory effects on NF-κB-mediated inflammatory response. However, the roles of VitE on mouse DC functions and the contribution of klotho to those effects both are unknown...
November 24, 2016: Biological Research
https://www.readbyqxmd.com/read/27879395/a-computationally-identified-compound-antagonizes-excess-fgf-23-signaling-in-renal-tubules-and-a-mouse-model-of-hypophosphatemia
#11
Zhousheng Xiao, Demian Riccardi, Hector A Velazquez, Ai L Chin, Charles R Yates, Jesse D Carrick, Jeremy C Smith, Jerome Baudry, L Darryl Quarles
Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23-induced activation of the FGFR/α-KL complex...
November 22, 2016: Science Signaling
https://www.readbyqxmd.com/read/27861640/association-of-high-density-lipoprotein-subclasses-with-chronic-kidney-disease-progression-atherosclerosis-and-klotho
#12
Eiichiro Kanda, Masumi Ai, Mitsuyo Okazaki, Masayuki Yoshida, Yoshitaka Maeda
BACKGROUND: Atherosclerosis is often a complication of chronic kidney disease (CKD) because of dyslipidemia and CKD-mineral and bone disorder. High-density lipoproteins (HDLs) are grouped into various subclasses composed of multiple proteins and lipids, and their transformation is altered in CKD. We investigated the roles of lipoprotein subclasses in CKD progression, and atherosclerosis, and the relationships with Klotho and fibroblast growth factor (FGF) 23. METHODS: Seventy-one CKD patients were enrolled in this prospective cohort study in Japan...
2016: PloS One
https://www.readbyqxmd.com/read/27859240/the-neuroprotective-effect-of-latanoprost-acts-via-klotho-mediated-suppression-of-calpain-activation-after-optic-nerve-transection
#13
Kotaro Yamamoto, Kota Sato, Masayoshi Yukita, Masayuki Yasuda, Kazuko Omodaka, Morin Ryu, Kosuke Fujita, Koji M Nishiguchi, Shigeki Machida, Toru Nakazawa
Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect. Klotho was firstly identified as the gene linked to the suppression of ageing phenotype: the defect of klotho gene in mice results ageing phenotype such as hypokinesis, arteriosclerosis and short lifespan...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27847255/fgf23-%C3%AE-klotho-as-a-paradigm-for-a-kidney-bone-network
#14
REVIEW
Makoto Kuro-O, Orson W Moe
The vertebrate endoskeleton is not a mere frame for muscle attachment to facilitate locomotion, but is a massive organ integrated with many physiologic functions including mineral and energy metabolism. Mineral balance is maintained by tightly controlled ion fluxes that are external (intestine and kidney) and internal (between bone and other organs), and are regulated and coordinated by many endocrine signals between these organs. The endocrine fibroblast growth factors (FGFs) and Klotho gene families are complex systems that co-evolved with the endoskeleton...
November 12, 2016: Bone
https://www.readbyqxmd.com/read/27847254/vascular-calcification-in-ckd-mbd-roles-for-phosphate-fgf23-and-klotho
#15
REVIEW
Shunsuke Yamada, Cecilia M Giachelli
Vascular calcification (VC) is highly prevalent in aging, diabetes mellitus, and chronic kidney disease (CKD). VC is a strong predictor of cardiovascular morbidity and mortality in the CKD population. Complex pathological mechanisms are involved in the development of VC, including osteochondrogenic differentiation and apoptosis of vascular smooth muscle cells, instability and release of extracellular vesicles loaded calcium and phosphate, and elastin degradation. Elevated serum phosphate is a late manifestation of CKD, and has been shown to accelerate mineral deposition in both the vessel wall and heart valves...
November 12, 2016: Bone
https://www.readbyqxmd.com/read/27844013/promoter-hypermethylation-of-klotho-an-anti-senescence-related-gene-in-colorectal-cancer-patients-of-kashmir-valley
#16
Malik Perveez, Malik Ajaz, Dil Afroze
Hypermethylation of CpG islands located in the promoter regions of genes is a major event in the development of the majority of cancer types, due to the subsequent aberrant silencing of important tumor suppressor genes. KLOTHO; a novel gene associated primarily with suppressing senescence has been shown to contribute to tumorigenesis as a result of its impaired function. Recently the relevance of KLOTHO promoter hypermethylation in colorectal carcinoma in humans has been reported. We analyzed the promoter hypermethylation of KLOTHO gene in 50 histopathologically confirmed tumor and adjacent normal tissues of colorectal cancer patients...
December 2015: Molecular Biology Research Communications
https://www.readbyqxmd.com/read/27837149/chronic-hyperphosphatemia-and-vascular-calcification-are-reduced-by-stable-delivery-of-soluble-klotho
#17
Julia M Hum, Linda M O'Bryan, Arun K Tatiparthi, Taryn A Cass, Erica L Clinkenbeard, Martin S Cramer, Manoj Bhaskaran, Robert L Johnson, Jonathan M Wilson, Rosamund C Smith, Kenneth E White
αKlotho (αKL) regulates mineral metabolism, and diseases associated with αKL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). αKL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and αKL-null mice...
November 11, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27818277/comparison-of-the-effects-of-novel-vitamin-d-receptor-analog-vs-105-and-paricalcitol-on-chronic-kidney-disease-mineral-bone-disorder-in-an-experimental-model-of-chronic-kidney-disease
#18
Hideki Fujii, Yuriko Yonekura, Kentaro Nakai, Keiji Kono, Shunsuke Goto, Shinichi Nishi
When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. We used male Sprague-Dawley (SD) rats and performed 5/6 nephrectomy at 8-9 weeks. At 10 weeks, the rats were classified into five groups and administered vehicle, low-dose paricalcitol (LP, 0...
November 3, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27808000/regulation-of-dendritic-cell-function-by-insulin-igf-1-pi3k-akt-signaling-through-klotho-expression
#19
Nguyen Thi Xuan, Nguyen Huy Hoang, Vu Phuong Nhung, Nguyen Thuy Duong, Nguyen Hai Ha, Nong Van Hai
Insulin or insulin-like growth factor 1 (IGF-1) promotes the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling in immune cells including dendritic cells (DCs), the most potent professional antigen-presenting cells for naive T cells. Klotho, an anti-aging protein, participates in the regulation of the PI3K/Akt signaling, thus the Ca(2+)-dependent migration is reduced in klotho-deficient DCs. The present study explored the effects of insulin/IGF-1 on DC function through klotho expression. To this end, the mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs)...
November 3, 2016: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27798196/klotho-suppresses-the-renin-angiotensin-system-in-adriamycin-nephropathy
#20
Tsuneo Takenaka, Tsutomu Inoue, Takashi Miyazaki, Hiroyuki Kobori, Akira Nishiyama, Naohito Ishii, Matsuhiko Hayashi, Hiromichi Suzuki
BACKGROUNDS: Klotho protein interacts with the transforming growth factor β (TGF-β) receptor and Wnt, which contribute to the progression of renal disease, inhibiting their signals. Renal and circulating klotho levels are diminished in chronic kidney disease. METHODS: Experiments were performed to assess whether supplementation of klotho protein could have protective effects on the kidney. Rats were injected with adriamycin (5 mg/kg) and divided into three groups: those treated with vehicle, those treated with klotho protein and those treated with klotho plus 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD)...
October 17, 2016: Nephrology, Dialysis, Transplantation
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