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KLOTHOS

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https://www.readbyqxmd.com/read/28076518/serum-klotho-but-not-haplotypes-associate-with-the-post-myocardial-infarction-status-of-older-adults
#1
Roberta S Paula, Vinícius C Souza, Wilcelly Machado-Silva, Bruno Ratier S Almeida, Andersen C Daros, Lucy Gomes, Aparecido P Ferreira, Ciro J Brito, Cláudio Córdova, Clayton F Moraes, Otávio T Nóbrega
OBJECTIVES: The number of deaths from vascular diseases is incredibly high worldwide, and reliable markers for major events are still needed. The current cross-sectional study investigated the association of Klotho haplotypes and Klotho serum levels with classic risk factors and a clinical history of vascular events. METHODS: Clinical, anthropometric, biochemical and nutritional assessments were conducted with 168 older adults, complemented by genotyping (rs9536314 and rs9527025) and the detection of serum Klotho (ELISA)...
December 1, 2016: Clinics
https://www.readbyqxmd.com/read/28069944/soluble-klotho-binds-monosialoganglioside-to-regulate-membrane-microdomains-and-growth-factor-signaling
#2
George Dalton, Sung-Wan An, Saif I Al-Juboori, Nicole Nischan, Joonho Yoon, Evgenia Dobrinskikh, Donald W Hilgemann, Jian Xie, Kate Luby-Phelps, Jennifer J Kohler, Lutz Birnbaumer, Chou-Long Huang
Soluble klotho, the shed ectodomain of the antiaging membrane protein α-klotho, is a pleiotropic endocrine/paracrine factor with no known receptors and poorly understood mechanism of action. Soluble klotho down-regulates growth factor-driven PI3K signaling, contributing to extension of lifespan, cardioprotection, and tumor inhibition. Here we show that soluble klotho binds membrane lipid rafts. Klotho binding to rafts alters lipid organization, decreases membrane's propensity to form large ordered domains for endocytosis, and down-regulates raft-dependent PI3K/Akt signaling...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28025385/prognostic-value-of-bone-and-vascular-derived-molecular-biomarkers-in-hemodialysis-and-renal-transplant-patients-a-systematic-review-and-meta-analysis
#3
Gernot Pichler, Maria C Haller, Alexander Kainz, Myles Wolf, Josep Redon, Rainer Oberbauer
BACKGROUND: Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent...
December 26, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28011195/protective-role-of-klotho-protein-on-epithelial-cells-upon-co-culture-with-activated-or-senescent-monocytes
#4
Jennifer Mytych, Izabela Wos, Przemyslaw Solek, Marek Koziorowski
Monocytes ensure proper functioning and maintenance of epithelial cells, while good condition of monocytes is a key factor of these interactions. Although, it was shown that in some circumstances, a population of altered monocytes may appear, there is no data regarding their effect on epithelial cells. In this study, using direct co-culture model with LPS-activated and Dox-induced senescent THP-1 monocytes, we reported for the first time ROS-induced DNA damage, reduced metabolic activity, proliferation inhibition and cell cycle arrest followed by p16-, p21- and p27-mediated DNA damage response pathways activation, premature senescence and apoptosis induction in HeLa cells...
December 21, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/28004977/establishment-of-transgenic-porcine-fibroblasts-expressing-a-human-klotho-gene-and-its-effects-on-gene-expression-and-preimplantation-development-of-cloned-embryos
#5
Sanghoon Lee, Joon Ho Moon, Kilyoung Song, Anukul Taweechaipaisankul, Young Kwang Jo, Hyun Ju Oh, Se Chang Park, Byeong Chun Lee
Even though the functions of the klotho gene in aging of small animals such as mice have been well investigated, studies using large animal models such as pigs, which have many similarities to humans, have been limited due to the absence of cell lines or animal models. Therefore, the objective of this study was to generate porcine cell lines overexpressing human klotho (hKlotho) and tetracycline (Tet)-inducible hKlotho and to produce cloned embryos from these cell lines. We designed vectors for hKlotho overexpression (CA-Klotho) under control of CMV enhancer/chicken β-actin (CAG) promoter and Tet-inducible hKlotho overexpression (Tet-Klotho, under control of doxycycline-dependent promoter)...
January 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28003041/the-impact-of-oat-avena-sativa-consumption-on-biomarkers-of-renal-function-in-patients-with-chronic-kidney-disease-a-parallel-randomized-clinical-trial
#6
Mohammad Hossein Rouhani, Mojgan Mortazavi Najafabadi, Pamela J Surkan, Ahmad Esmaillzadeh, Awat Feizi, Leila Azadbakht
BACKGROUND & OBJECTIVE: Animal studies report that oat (Avena sativa L) intake has favorable effects on kidney function. However, the effects of oat consumption have not been assessed in humans. The aim of this study was to examine the impact of oat intake on biomarkers of renal function in patients with chronic kidney disease (CKD). METHODS: Fifty-two patients with CKD were randomly assigned to a control group (recommended to reduce intake of dietary protein, phosphorus, sodium and potassium) or an oat consumption group (given nutritional recommendations for controls +50 g/day oats)...
December 2, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28000180/reduction-of-calprotectin-and-phosphate-during-testosterone-therapy-in-aging-men-a-randomized-controlled-trial
#7
L Pedersen, L L Christensen, S M Pedersen, M Andersen
OBJECTIVES: To investigate the effect of testosterone treatment on biomarkers calprotectin, fibroblast growth factor 23 (FGF23), soluble Klotho, phosphate, calcium, parathyroid hormone, creatinine and estimated glomerular filtration rate. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: Odense Androgen Study-the effect of Testim and training in hypogonadal men. PARTICIPANTS: Men aged 60-78 years old with a low normal concentration of free of bioavailable testosterone <7...
December 20, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27999806/changes-in-serum-concentrations-of-fibroblast-growth-factor-23-and-soluble-klotho-in-hemodialysis-patients-after-total-parathyroidectomy
#8
Shang-Chih Liao, Sin-Hua Moi, Fong-Fu Chou, Cheng-Hong Yang, Jin-Bor Chen
Background. We examined the changes in circulating fibroblast growth factor 23 (FGF23) and Klotho concentrations in hemodialysis patients after parathyroidectomy (PTX). Methods. We enrolled a cohort of hemodialysis patients who received PTX. Postoperatively, patients received calcium supplements and/or vitamin D analogue (calcitriol) to maintain serum calcium within 7.0-8.0 mg/dL. Information on clinical parameters including bone-mineral metabolic variables was collected pre-PTX and on days 5 and 90 after PTX...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27979597/inhibition-of-trpc6-channels-ameliorates-renal%C3%A2-fibrosis-and-contributes-to-renal-protection%C3%A2-by%C3%A2-soluble-klotho
#9
Yueh-Lin Wu, Jian Xie, Sung-Wan An, Noelynn Oliver, Nestor X Barrezueta, Mei-Hsiang Lin, Lutz Birnbaumer, Chou-Long Huang
Fibrosis is an exaggerated form of tissue repair that occurs with serious damage or repetitive injury and ultimately leads to organ failure due to the excessive scarring. Increased calcium ion entry through the TRPC6 channel has been associated with the pathogenesis of heart and glomerular diseases, but its role in renal interstitial fibrosis is unknown. We studied this by deletion of Trpc6 in mice and found it decreased unilateral ureteral obstruction-induced interstitial fibrosis and blunted increased mRNA expression of fibrosis-related genes in the ureteral obstructed kidney relative to that in the kidney of wild-type mice...
December 12, 2016: Kidney International
https://www.readbyqxmd.com/read/27959617/senescence-in-copd-and-its-comorbidities
#10
Peter J Barnes
Chronic obstructive pulmonary disease (COPD) is regarded as a disease of accelerated lung aging. This affliction shows all of the hallmarks of aging, including telomere shortening, cellular senescence, activation of PI3 kinase-mTOR signaling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence, and a low-grade chronic inflammation (inflammaging). Many of these pathways are driven by chronic exogenous and endogenous oxidative stress...
December 9, 2016: Annual Review of Physiology
https://www.readbyqxmd.com/read/27951565/klotho-as-a-therapeutic-target-during-the-development-of-renal-fibrosis
#11
Shigehiro Doi, Takao Masaki
Systemic symptoms such as the ectopic calcification, atrophy of skin and muscle, and impaired sexual function observed in chronic kidney diseases (CKD) have been reported to coincide with those observed in geriatric symptoms. Regarding the kidney, clinical/pathological characteristics in CKD patients also coincide with those in the aging kidney. These findings suggest common mechanisms in the development of both CKD and aging. Our investigation of aging factors associated with renal fibrosis in IgA nephropathy patients revealed a significant correlation between accumulation of cells with an arrested cell cycle and decreased expression of Klotho protein...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/27941640/fibroblast-growth-factor-23-a-potential-uremic-toxin
#12
REVIEW
Piotr Kuczera, Marcin Adamczak, Andrzej Wiecek
Fibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)₂-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate...
December 8, 2016: Toxins
https://www.readbyqxmd.com/read/27941311/%C3%AE-klotho-as-a-negative-regulator-of-the-peptide-transporters-pept1-and-pept2
#13
Abeer Abousaab, Jamshed Warsi, Madhuri S Salker, Florian Lang
BACKGROUND/AIMS: β-Klotho, a transmembrane protein expressed in several tissues including the brain and the kidney, is critically important for inhibition of 1,25(OH)2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. Soluble klotho is a β-glucuronidase participating in the regulation of several ion channels and carriers. The present study explored the effect of β-Klotho protein on the peptide transporters PEPT1 and PEPT2...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27934558/fibroblast-growth-factor-23-in-postrenal-transplant-an-often-forgotten-hormone
#14
Fateme Shamekhi Amiri, Mohammad Reza Khatami
Fibroblast growth factor 23 is likely to be the most important regulator of phosphate homeostasis, which mediates its functions through fibroblast growth factor receptors and the coreceptor Klotho. In addition to reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, fibroblast growth factor 23 inhibits renal 1α-hydroxylase and stimulates 24-hydroxylase and appears to reduce parathyroid hormone secretion in short-term studies. Fibroblast growth factor 23 synthesis and secretion by osteocytes and osteoblasts are upregulated through 1,25-dihydroxyvitamin D3 and through an increased dietary phosphate intake...
December 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27931585/resveratrol-ameliorated-vascular-calcification-by-regulating-sirt-1-and-nrf2
#15
P Zhang, Y Li, Y Du, G Li, L Wang, F Zhou
Pathologic vascular calcification is a significant reason for mortality and morbidity in patients who suffer from end-stage renal disease (ESRD). Resveratrol, a scavenger for many free radicals, is a crucial compound for biomedicine. However, the role and mechanism of resveratrol in vascular calcification is still unknown. In this study, to mimic vascular calcification in ESRD, we used β-glyceophosphate to stimulate the rat vascular smooth muscle cells (RASMCs). We investigate the therapeutic role of resveratrol pretreatment in vascular calcification...
December 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27929669/fgf23-is-not-required-to-regulate-fetal-phosphorus-metabolism-but-exerts-effects-within-12-hours-after-birth
#16
Yue Ma, Beth J Kirby, Nicholas A Fairbridge, Andrew C Karaplis, Beate Lanske, Christopher S Kovacs
Loss of fibroblast growth factor 23 (FGF23) causes hyperphosphatemia, extraskeletal calcifications, and early mortality; excess FGF23 causes hypophosphatemia with rickets or osteomalacia. However, FGF23 may not be important during fetal development. FGF23 deficiency (Fgf23 null) and FGF23 excess (Phex null) did not alter fetal phosphorus or skeletal parameters. In this study we further tested our hypothesis that FGF23 is not essential for fetal phosphorus regulation but becomes important after birth. Although co-receptor Klotho null adults have extremely high FGF23 concentrations, intact FGF23 was normal in Klotho null fetuses, as were fetal phosphorus and skeletal parameters, and placental and renal expression of FGF23 target genes...
December 8, 2016: Endocrinology
https://www.readbyqxmd.com/read/27920796/neutrophil-gelatinase-associated-lipocalin-fibroblast-growth-factor-23-and-soluble-klotho-in-long-term-kidney-donors
#17
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
#18
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
#19
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...
February 2017: 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
#20
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...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
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