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soluble klotho protein

Qing-Ya Zeng, Zhi-Yin Xia, Yan-Shan Tong, Liang Sun, Hong-Bin Mou, Rui Chen, Guang-Yu Bi, Chang-Hua Liu
BACKGROUND: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown. METHODS: 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: hemodialysis (A1, n=52), peritoneal dialysis (A2, n=30), and non-dialysis (A3, n=55). The Klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble Klotho protein (sKL) and fibroblast growth factor (FGF23)...
December 8, 2018: Nephrology
Ming Chang Hu, Mingjun Shi, Orson W Moe
Alpha-Klotho is a member of the Klotho family consisting of two other single-pass transmembrane proteins: βKlotho and γKlotho; αKlotho has been shown to circulate in the blood. Fibroblast growth factor (FGF)23 is a member of the FGF superfamily of 22 genes/proteins. αKlotho serves as a co-receptor with FGF receptors (FGFRs) to provide a receptacle for physiological FGF23 signaling including regulation of phosphate metabolism. The extracellular domain of transmembrane αKlotho is shed by secretases and released into blood circulation (soluble αKlotho)...
December 1, 2018: Pflügers Archiv: European Journal of Physiology
L Darryl Quarles
PURPOSE OF REVIEW: The current review examines what is known about the FGF-23/α-Klotho co-dependent and independent pathophysiological effects, and whether FGF-23 and/or α-Klotho are potential therapeutic targets. RECENT FINDINGS: FGF-23 is a hormone derived mainly from bone, and α-Klotho is a transmembrane protein. Together they form a trimeric signaling complex with FGFRs in target tissues to mediate the physiological functions of FGF-23. Local and systemic factors control FGF-23 release from osteoblast/osteocytes in bone, and circulating FGF-23 activates FGFR/α-Klotho complexes in kidney proximal and distal renal tubules to regulate renal phosphate excretion, 1,25 (OH)2D metabolism, sodium and calcium reabsorption, and ACE2 and α-Klotho expression...
January 2019: Current Opinion in Nephrology and Hypertension
Sven-Jean Tan, Melissa M Chu, Nigel D Toussaint, Michael Mx Cai, Tim D Hewitson, Stephen G Holt
The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated...
January 2018: Journal of Circulating Biomarkers
Laura Kranaster, Carolin Hoyer, Suna S Aksay, J Malte Bumb, Norbert Müller, Peter Zill, Markus J Schwarz, Natalie Moll, Beat Lutz, Laura Bindila, Inga Zerr, Matthias Schmitz, Kaj Blennow, Henrik Zetterberg, Dieter Haffner, Maren Leifheit-Nestler, Cagakan Ozbalci, Christoph Janke, Manfred Thiel, Alexander Sartorius
BACKGROUND: No candidate biomarkers based on cerebrospinal fluid (CSF) have been identified as prognostic factors in patients with major depression treated with electroconvulsive therapy (ECT), yet. METHOD: Following different underlying hypotheses, we analysed baseline CSF levels of markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system (interleukin [IL]-6, neopterin, soluble CD14, soluble CD163, migration inhibitory factor and monocyte chemotactic protein 1), endocannabinoids, sphingolipids and Klotho before ECT in patients with depression (n = 12) to identify possible correlations with the clinical antidepressant response to ECT...
2019: Neuropsychobiology
Ling Yu, Li Kang, Xiao-Zhuan Ren, Zong-Li Diao, Wen-Hu Liu
BACKGROUND/AIMS: Serum soluble Klotho (sKlotho) plays a role in cardiovascular disease in some populations. However, information regarding the effect of serum sKlotho on atherosclerosis in patients on maintenance hemodialysis (MHD) is limited. Therefore, we tested the level of serum sKlotho in MHD patients to investigate atherosclerosis disease and determine the relationship between sKlotho and atherosclerosis. METHODS: Using cross-sectional research, anthropometric and laboratory data were collected for 330 MHD patients...
2018: Kidney & Blood Pressure Research
L-C Desbiens, A Sidibé, R-V Ung, C Fortier, M Munger, Y-P Wang, S-K Bisson, K Marquis, M Agharazii, F Mac-Way
We performed a case-control study on 130 age- and sex-matched hemodialysis patients. In multivariate analysis, we observed that FGF23 levels were associated with fracture incidence and that soluble α-klotho levels were associated with the aortic-brachial arterial stiffness ratio. INTRODUCTION: New bone markers such as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23), and α-klotho have been identified as potential key players in bone and vascular abnormalities of chronic kidney disease...
October 2018: Osteoporosis International
Shubei Zheng, Yu Zheng, Lingwei Jin, Zhihong Zhou, Zhanyuan Li
Background: We aimed to investigate the relationship between serum soluble Klotho protein (sKlotho) level and coronary artery calcification (CAC) as well as prognosis in patients with maintenance hemodialysis (MHD). Methods: Overall, 128 adult patients with end-stage renal failure treated with MHD were collected in the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, China in 2013. Serum sKlotho was detected by ELISA and coronary artery calcification was measured by multi-slice spiral computed tomography (MSCT)...
April 2018: Iranian Journal of Public Health
Reinhold G Erben
PURPOSE OF REVIEW: α-Klotho (Klotho) occurs in three isoforms, a membrane-bound form acting as a coreceptor for fibroblast growth factor-23 (FGF23) signalling, a shed soluble form consisting of Klotho's large ectodomain thought to act as an enzyme or a hormone, and a secreted truncated form generated by alternative splicing of the Klotho mRNA with unknown function. The purpose of this review is to highlight the recent advances in our understanding of Klotho's function in mineral homeostasis...
July 2018: Current Opinion in Nephrology and Hypertension
Lulu Ma, Min Gao, Lin Wu, Xiufen Zhao, Huijuan Mao, Changying Xing
Fibroblastic growth factor 23 (FGF23) is a hormone secreted primarily by bone. FGF23 is elevated in the serum of chronic kidney disease (CKD) patients, but the exact mechanism is not well known. Klotho is identified as an aging suppressor, which is mainly expressed in the kidney, and the level of soluble Klotho is negatively associated with FGF23 in CKD. The aim of this study was to investigate the effect and possible mechanism of Klotho on FGF23 synthesis in osteoblast-like UMR-106 cells. UMR-106 cells were divided into five groups: (i) control group; (ii) β-glycerophosphate (β-GP) group; (iii) β-GP + Klotho group; (iv) β-GP+ lithium chloride (LiCl, a Wnt/β-catenin pathway agonist) group; and (v) β-GP + Klotho + LiCl group...
May 30, 2018: Cell Biology International
G Poelzl, S K Ghadge, M Messner, B Haubner, Ph Wuertinger, A Griesmacher, J Doerler, C Ensinger, H Ulmer, M M Zaruba
Klotho is an antiaging protein which exerts known cardioprotection. In kidney, trans-membrane Klotho acts as essential co-receptor of fibroblast growth factor 23 (FGF23). In the heart, soluble Klotho (sKlotho) protects from systolic dysfunction independently of FGF23. Here, we analyzed the association of FGF23 and sKlotho upon progression of chronic heart failure (CHF) and analyzed Klotho expression in human hearts. Serum levels of sKlotho and FGF23 were measured in 287 patients with cardiomyopathy (CMP). Tissue samples from CMP (n = 10) and healthy control hearts (n = 10) were analyzed for Klotho mRNA and protein expression...
May 30, 2018: Scientific Reports
Emilio González-Reimers, Lucía Romero-Acevedo, Elisa Espelosín-Ortega, M Candelaria Martín-González, Geraldine Quintero-Platt, Pedro Abreu-González, María José de-la-Vega-Prieto, Daniel Martínez-Martínez, Francisco Santolaria-Fernández
Aim: Fibroblast growth factor (FGF-23) and α-Klotho (Klotho) levels may be altered in inflammatory conditions, possibly as compensatory mechanisms. Klotho exerts a protective effect on neurodegeneration and improves learning and cognition. No data exist about the association of Klotho and FGF-23 levels with brain atrophy observed in alcoholics. The aim of this study is to explore these relationships. Short summary: FGF-23 and Klotho levels are altered in inflammation, possibly as compensatory mechanisms...
September 1, 2018: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
Jing Qian, Jianyong Zhong, Minhua Yan, Ping Cheng, Huizhu Shi, Chuanming Hao, Yong Gu, Lingyun Lai
BACKGROUND/AIMS: We aimed to determine if soluble α-klotho level was an indicator of chronic kidney disease (CKD) progression and whether α-klotho interacted with aldosterone during the course of further renal damage. METHODS: 112 adults with stages 1-5 CKD were enrolled into our cohort study. All of the patients were followed up for 6 years (from January 2010 to December 2015). Serum soluble α-klotho and aldosterone were measured at baseline and at 1.5-years follow-up...
2018: Kidney & Blood Pressure Research
Naomi C Boisvert, Chet E Holterman, Alexey Gutsol, Josée Coulombe, Wanling Pan, R Todd Alexander, Douglas A Gray, Chris R Kennedy
Loss of ubiquitin COOH-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme required for neuronal function, led to hyperphosphatemia accompanied by phosphaturia in mice, while calcium homeostasis remained intact. We therefore investigated the mechanisms underlying the phosphate imbalance in Uchl1-/- mice. Interestingly, phosphaturia was not a result of lower renal brush border membrane sodium-phosphate cotransporter expression as sodium-phosphate cotransporter 2a and 2c expression levels was similar to wild-type levels...
August 1, 2018: American Journal of Physiology. Renal Physiology
Hyo Jin Kim, Eunjeong Kang, Yun Kyu Oh, Yeong Hoon Kim, Seung Hyeok Han, Tae Hyun Yoo, Dong-Wan Chae, Joongyub Lee, Curie Ahn, Kook-Hwan Oh
BACKGROUND: Klotho, a protein linked to aging, has emerged as a pivotal player in mineral bone metabolism and might explain the relationship between chronic kidney disease (CKD) and cardiovascular disease (CVD). The present study aimed to investigate the association between serum klotho and cardiac parameters from a large-scale Korean CKD cohort. METHODS: We analyzed 2101 participants from KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort who had been measured for serum klotho levels...
March 5, 2018: BMC Nephrology
Caio H Mazucanti, Elisa M Kawamoto, Mark P Mattson, Cristoforo Scavone, Simonetta Camandola
Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknown. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase...
March 1, 2018: Journal of Cerebral Blood Flow and Metabolism
George D Dalton, Jian Xie, Sung-Wan An, Chou-Long Huang
The klotho gene encodes a type I single-pass transmembrane protein that contains a large extracellular domain, a membrane spanning segment, and a short intracellular domain. Klotho protein exists in several forms including the full-length membrane form (mKl) and a soluble circulating form [soluble klotho (sKl)]. mKl complexes with fibroblast growth factor receptors to form coreceptors for FGF23, which allows it to participate in FGF23-mediated signal transduction and regulation of phosphate and calcium homeostasis...
2017: Frontiers in Endocrinology
Xi Kuang, Hong-Jing Zhou, Amy H Thorne, Xi-Nan Chen, Lin-Jiao Li, Jun-Rong Du
Emerging evidence suggests that alpha-processing single transmembrane proteins, amyloid precursor protein (APP) and anti-aging protein Klotho, are likely to be involved in the progression of Alzheimer's disease (AD). The natural phthalide Ligustilide (LIG) has been demonstrated to protect against aging- and amyloid-β (Aβ)-induced brain dysfunction in animal models. The present study is to investigate the effects of LIG on cognitive deficits and metabolism of both APP and Klotho and its underlying mechanism in AD double-transgenic (APP/PS1) mice and cultured human cells...
2017: Frontiers in Aging Neuroscience
Stefanie Krick, Nathalie Baumlin, Sheyla Paredes Aller, Carolina Aguiar, Alexander Grabner, Juliette Sailland, Eliana Mendes, Andreas Schmid, Lixin Qi, Nicolae V David, Patrick Geraghty, Gwendalyn King, Susan E Birket, Steven M Rowe, Christian Faul, Matthias Salathe
Chronic inflammation is a hallmark of cystic fibrosis (CF) and associated with increased production of transforming growth factor (TGF) β and interleukin (IL)-8. α-klotho (KL), a transmembrane or soluble protein, functions as a co-receptor for Fibroblast Growth Factor (FGF) 23, a known pro-inflammatory, prognostic marker in chronic kidney disease. KL is downregulated in airways from COPD patients. We hypothesized that both KL and FGF23 signaling modulate TGF β-induced IL-8 secretion in CF bronchial epithelia...
October 30, 2017: Scientific Reports
Rik Mencke, Geert Harms, Jill Moser, Matijs van Meurs, Arjan Diepstra, Henri G Leuvenink, Jan-Luuk Hillebrands
Klotho is a renal protein involved in phosphate homeostasis, which is downregulated in renal disease. It has long been considered an antiaging factor. Two Klotho gene transcripts are thought to encode membrane-bound and secreted Klotho. Indeed, soluble Klotho is detectable in bodily fluids, but the relative contributions of Klotho secretion and of membrane-bound Klotho shedding are unknown. Recent advances in RNA surveillance reveal that premature termination codons, as present in alternative Klotho mRNA (for secreted Klotho), prime mRNAs for degradation by nonsense-mediated mRNA decay (NMD)...
October 19, 2017: JCI Insight
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