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KLOTHOS

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https://www.readbyqxmd.com/read/28812223/prognostic-potential-of-klotho-and-sfrp1-promoter-methylation-in-head-and-neck-squamous-cell-carcinoma
#1
Abeer A Alsofyani, Rawiah A Alsiary, Alaa Samkari, Baraa T Alhaj-Hussain, Jalaluddin Azam Khan, Jaudah Al-Maghrabi, Aisha Elaimi, Mohammed H Al-Qahtani, Adel M Abuzenadah, Ashraf Dallol
Hypermethylation in the CpG island promoter regions of tumor suppressors is known to play a significant role in the development of HNSCC and the detection of which can aid the classification and prognosis of HNSCC. This study aims to profile the methylation patterns in a panel of key genes including CDKN2A, CDKN2B, KLOTHO (KL), RASSF1A, RARB, SLIT2, and SFRP1, in a group of HNSCC samples from Saudi Arabia. The extent of methylation in these genes is determined using the MethyLight assay and correlated with known clinicopathological parameters in our samples of 156 formalin-fixed and paraffin-embedded HNSCC tissues...
August 16, 2017: Journal of Applied Genetics
https://www.readbyqxmd.com/read/28807259/is-osteocyte-klotho-bad-for-bone-health
#2
Rosa M A Moysés, Adriana Dusso
The recent identification of αKlotho protein (Klotho) in osteocytes led to the generation of an experimental mouse model with osteocyte-specific Klotho ablation. This enabled Komaba et al. to assess the contribution to bone structure and function of osteocyte Klotho per se as compared with that of the systemic fibroblast growth factor 23-Klotho axis. Surprisingly, unlike the osteopenia and low bone turnover of systemic Klotho deletion, osteocyte-specific Klotho ablation resulted in increased osteoblastic activity and bone formation rate...
September 2017: Kidney International
https://www.readbyqxmd.com/read/28806578/klotho-dysfunction-a-pathway-linking-the-aging-process-to-bipolar-disorder
#3
Izabela Guimarães Barbosa, Natalia Pessoa Rocha, Gokay Alpak, Erica Leandro Marciano Vieira, Rodrigo Barreto Huguet, Fabio Lopes Rocha, Breno Satler de Oliveira Diniz, Antonio Lucio Teixeira
AIM: Although accelerated aging profile has been described in bipolar disorder (BD), the biology linking BD and aging is still largely unknown. Reduced levels and/or activity of a protein named Klotho is associated with decreased life span, premature aging and occurrence of age-related diseases. Therefore, this study was designed to evaluate plasma levels of Klotho in BD patients and controls. METHODS: Forty patients with type 1 BD and 30 controls were enrolled in this study...
August 11, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28805483/tet1-mediated-dna-demethylation-involves-in-neuron-damage-induced-by-bilirubin-in-vitro
#4
Panhong Gou, Xiaoling Qi, Rui Yuan, Haojie Li, Xiaoling Gao, Junling Wang, Benzhong Zhang
The aim of this study is to identify the role of Tet1-mediated DNA demethylation in the neurotoxicity caused by unconjugated bilirubin (UCB) in vitro. Primary neuronal cells after cultured for 72 h were exposed to UCB (0-100 μmol/L) for 24 h. Following exposure to UCB cytotoxicity was determined with the methyl tetrazolium (MTT) assay, reactive oxygen species (ROS) and caspase-3 activity in neuron cells were measured with the corresponding assay kits. The expression of Tet1 and Klotho was determined with RT-PCR at mRNA level and western blot at protein level...
August 14, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28798354/enpp1-is-an-anti-aging-factor-that-regulates-klotho-under-phosphate-overload-conditions
#5
Ryuichi Watanabe, Nobuyuki Fujita, Yuiko Sato, Tami Kobayashi, Mayu Morita, Takatsugu Oike, Kana Miyamoto, Makoto Kuro-O, Toshimi Michigami, Seiji Fukumoto, Takashi Tsuji, Yoshiaki Toyama, Masaya Nakamura, Morio Matsumoto, Takeshi Miyamoto
Control of phosphate metabolism is crucial to regulate aging in mammals. Klotho is a well-known anti-aging factor that regulates phosphate metabolism: mice mutant or deficient in Klotho exhibit phenotypes resembling human aging. Here we show that ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) is required for Klotho expression under phosphate overload conditions. Loss-of-function Enpp1 (ttw/ttw) mice under phosphate overload conditions exhibited phenotypes resembling human aging and Klotho mutants, such as short life span, arteriosclerosis and osteoporosis, with elevated serum 1,25(OH)2D3 levels...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796175/suppression-of-wnt-signaling-and-osteogenic-changes-in-vascular-smooth-muscle-cells-by-eicosapentaenoic-acid
#6
Yukihiro Saito, Kazufumi Nakamura, Daiji Miura, Kei Yunoki, Toru Miyoshi, Masashi Yoshida, Norifumi Kawakita, Tomonari Kimura, Megumi Kondo, Toshihiro Sarashina, Satoshi Akagi, Atsuyuki Watanabe, Nobuhiro Nishii, Hiroshi Morita, Hiroshi Ito
Vascular medial calcification is often observed in patients with arteriosclerosis. It is also associated with systolic hypertension, wide pulse pressure, and fluctuation of blood pressure, which results in cardiovascular events. Eicosapentaenoic acid (EPA) has been shown to suppress vascular calcification in previous animal experiments. We investigated the inhibitory effects of EPA on Wnt signaling, which is one of the important signaling pathways involved in vascular calcification. Intake of food containing 5% EPA resulted in upregulation of the mRNA expression of Klotho, an intrinsic inhibitor of Wnt signaling, in the kidneys of wild-type mice...
August 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28795324/the-fgf23-klotho-axis-and-cardiac-tissue-doppler-imaging-in-pediatric-chronic-kidney-disease-a-prospective-cohort-study
#7
Ylva Tranæus Lindblad, Hannes Olauson, Georgios Vavilis, Ulf Hammar, Maria Herthelius, Jonas Axelsson, Peter Bárány
BACKGROUND: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. METHODS: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1...
August 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28793260/peripheral-elevation-of-a-klotho-fragment-enhances-brain-function-and-resilience-in-young-aging-and-%C3%AE-synuclein-transgenic-mice
#8
Julio Leon, Arturo J Moreno, Bayardo I Garay, Robert J Chalkley, Alma L Burlingame, Dan Wang, Dena B Dubal
Cognitive dysfunction and decreased mobility from aging and neurodegenerative conditions, such as Parkinson and Alzheimer diseases, are major biomedical challenges in need of more effective therapies. Increasing brain resilience may represent a new treatment strategy. Klotho, a longevity factor, enhances cognition when genetically and broadly overexpressed in its full, wild-type form over the mouse lifespan. Whether acute klotho treatment can rapidly enhance cognitive and motor functions or induce resilience is a gap in our knowledge of its therapeutic potential...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28780894/gene-therapy-for-hypertension
#9
Ludovit Paulis, Heinrich Franke, Fedor Simko
The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: The authors have searched for studies using gene therapy in hypertension reporting BP outcomes. They have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents...
August 7, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28771600/eicosapentaenoic-acid-prevents-arterial-calcification-in-klotho-mutant-mice
#10
Kazufumi Nakamura, Daiji Miura, Yukihiro Saito, Kei Yunoki, Yasushi Koyama, Minoru Satoh, Megumi Kondo, Kazuhiro Osawa, Omer F Hatipoglu, Toru Miyoshi, Masashi Yoshida, Hiroshi Morita, Hiroshi Ito
BACKGROUND: The klotho gene was identified as an "aging-suppressor" gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated. The aim of this study was to determine the effect of EPA on arterial calcification in klotho mutant mice...
2017: PloS One
https://www.readbyqxmd.com/read/28771227/klotho-enhances-foxo3-mediated-manganese-superoxide-dismutase-expression-by-negatively-regulating-pi3k-akt-pathway-during-tacrolimus-induced-oxidative-stress
#11
Sun Woo Lim, Long Jin, Kang Luo, Jian Jin, Yoo Jin Shin, Sung Yi Hong, Chul Woo Yang
Mammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28761977/calcineurin-inhibitors-regulate-fibroblast-growth-factor-23-fgf23-synthesis
#12
Ludmilla Bär, Claudia Großmann, Michael Gekle, Michael Föller
Fibroblast growth factor 23 (FGF23) inhibits renal phosphate reabsorption and calcitriol formation, effects depending on Klotho as a co-receptor for FGF23. In addition, FGF23/Klotho strongly influences aging and the onset of age-associated diseases. The synthesis of FGF23 by bone cells is induced by store-operated Ca(2+) entry (SOCE) through Orai1 in UMR106 osteoblast-like cells. Ca(2+) entry activates the phosphatase calcineurin in many cell types which dephosphorylates nuclear factor of activated T cells (NFAT) thereby stimulating its transcriptional activity...
July 31, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28754744/klb-encoding-%C3%AE-klotho-is-mutated-in-patients-with-congenital-hypogonadotropic-hypogonadism
#13
Cheng Xu, Andrea Messina, Emmanuel Somm, Hichem Miraoui, Tarja Kinnunen, James Acierno, Nicolas J Niederländer, Justine Bouilly, Andrew A Dwyer, Yisrael Sidis, Daniele Cassatella, Gerasimos P Sykiotis, Richard Quinton, Christian De Geyter, Mirjam Dirlewanger, Valérie Schwitzgebel, Trevor R Cole, Andrew A Toogood, Jeremy Mw Kirk, Lacey Plummer, Urs Albrecht, William F Crowley, Moosa Mohammadi, Manuel Tena-Sempere, Vincent Prevot, Nelly Pitteloud
Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic form of isolated gonadotropin-releasing hormone (GnRH) deficiency caused by mutations in > 30 genes. Fibroblast growth factor receptor 1 (FGFR1) is the most frequently mutated gene in CHH and is implicated in GnRH neuron development and maintenance. We note that a CHH FGFR1 mutation (p.L342S) decreases signaling of the metabolic regulator FGF21 by impairing the association of FGFR1 with β-Klotho (KLB), the obligate co-receptor for FGF21. We thus hypothesized that the metabolic FGF21/KLB/FGFR1 pathway is involved in CHH Genetic screening of 334 CHH patients identified seven heterozygous loss-of-function KLB mutations in 13 patients (4%)...
July 28, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28745688/-risk-factors-for-anemia-in-the-early-stages-of-chronic-kidney-disease
#14
Yu S Milovanov, L V Kozlovskaya, L Yu Milovanova, M M Markina, V V Kozlov, M V Taranova, V V Fomin
AIM: To identify the early markers of anemia in chronic kidney disease (CKD) in patients with chronic glomerulonephritis (CGN) and glomerulonephritis (GN) in systemic diseases. SUBJECTS AND METHODS: Seventy-nine patients with some male preponderance who were aged 21 to 65 years (45.3±11.1 years) and had CKD (CGN and GN) in systemic diseases (systemic lupus erythematosus and Wegener's granulomatosis) in the early stages (Stages I-II) of CKD were examined. GN was diagnosed by a lifetime renal biopsy...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28745686/-effects-of-keto-amino-acids-and-a-low-protein-diet-on-the-nutritional-status-of-patients-with-stages-3b-4-chronic-kidney-disease
#15
S Yu Milovanova, Yu S Milovanov, M V Taranova, I A Dobrosmyslov
AIM: To evaluate the efficacy of keto/amino acids in maintaining protein balance and preventing mineral metabolic disturbances and the development of uremic hyperparathyroidism in the long-term use of a low-protein diet (LPD) in patients with Stages 3B-4 chronic kidney disease (CKD). SUBJECTS AND METHODS: Ninety patients with CKD caused by chronic latent glomerulonephritis in 65 patients and chronic tubulointerstitial nephritis of various etiologies (gout, drug-induced, and infection) in 25 were examined...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28743343/-effects-of-multimodal-combination-dialysis-on-klotho-protein-fgf-23-and-bnp-in-patients-with-maintenance-hemodialysis
#16
Xiaofeng Deng, Qing Dai, Li Wan, Ling Tang, Yue Shu, Hengfen Xiao, Yuanyuan Bi, Hongfen Yang
OBJECTIVE: To discuss the effects of multimodal combination dialysis on Klotho protein, fibroblast growth factor-23 (FGF-23) and brain natriuretic peptide (BNP) in patients with maintenance hemodialysis (MHD). METHODS: A randomized controlled trial (RCT) was conducted. 120 patients who was diagnosed with chronic renal failure (CRF) uremia receiving MHD over 3 months admitted to Blood Purification Centre of Department of Nephrology of the Second People's Hospital of Guiyang from December 2015 to December 2016 were enrolled, who were randomly divided into hemodialysis (HD) group (HD for 8 times a month), HD + hemofiltration (HF) group (HD for 8 times a month + HF once a month), and HD + HF + hemoperfusion (HP) group (HD for 8 times a month + HF for 4 times a month + HP once a month), with 40 patients in each group...
July 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28728941/comparison-of-calcimimetic-r568-and-calcitriol-in-mineral-homeostasis-in-the-hyp-mouse-a-murine-homolog-of-x-linked-hypophosphatemia
#17
Maren Leifheit-Nestler, Julia Kucka, Emi Yoshizawa, Geert Behets, Patrick D'Haese, Christian Bergen, Martin Meier, Dagmar-Christiane Fischer, Dieter Haffner
X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)2D3 (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health...
July 18, 2017: Bone
https://www.readbyqxmd.com/read/28709936/effects-of-klotho-on-fibrosis-and-cancer-a-renal-focus-on-mechanisms-and-therapeutic-strategies
#18
Rik Mencke, Hannes Olauson, Jan-Luuk Hillebrands
Klotho is a membrane-bound protein predominantly expressed in the kidney, where it acts as a permissive co-receptor for Fibroblast Growth Factor 23. In its shed form, Klotho exerts anti-fibrotic effects in several tissues. Klotho-deficient mice spontaneously develop fibrosis and Klotho deficiency exacerbates the disease progression in fibrotic animal models. Furthermore, Klotho overexpression or supplementation protects against fibrosis in various models of renal and cardiac fibrotic disease. These effects are mediated at least partially by the direct inhibitory effects of soluble Klotho on TGFβ1 signaling, Wnt signaling, and FGF2 signaling...
July 11, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28701312/inflammation-and-premature-aging-in-advanced-chronic-kidney-disease
#19
Jeroen Kooman, Marijke Dekker, Len A Usvyat, Peter Kotanko, Frank Van der Sande, Casper G Schalkwijk, Paul G Shiels, Peter Stenvinkel
Systemic inflammation in end-stage renal disease (ESRD) is an established risk factor for mortality and a catalyst for other complications which are related to a premature aging phenotype, including muscle wasting, vascular calcification and other forms of premature vascular disease, depression, osteoporosis and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have direct effect on cellular and tissue function...
July 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28694529/the-production-of-fibroblast-growth-factor-23-is-controlled-by-tgf-%C3%AE-2
#20
Martina Feger, Philipp Hase, Bingbing Zhang, Frank Hirche, Philipp Glosse, Florian Lang, Michael Föller
Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions...
July 10, 2017: Scientific Reports
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