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https://www.readbyqxmd.com/read/28215989/klotho-regulates-ca1-hippocampal-synaptic-plasticity
#1
Qin Li, Hai T Vo, Jing Wang, Stephanie Fox-Quick, Lynn E Dobrunz, Gwendalyn D King
Global klotho overexpression extends lifespan while global klotho-deficiency shortens it. As well, klotho protein manipulations inversely regulate cognitive function. Mice without klotho develop rapid onset cognitive impairment before they are 2months old. Meanwhile, adult mice overexpressing klotho show enhanced cognitive function, particularly in hippocampal-dependent tasks. The cognitive enhancing effects of klotho extend to humans with a klotho polymorphism that increases circulating klotho and executive function...
February 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28212442/ecto-5-nucleotidase-cd73-nt5e-vitamin-d-receptor-and-fgf23-gene-polymorphisms-may-play-a-role-in-the-development-of-calcific-uremic-arteriolopathy-in-dialysis-patients-data-from-the-german-calciphylaxis-registry
#2
Hansjörg Rothe, Vincent Brandenburg, Margot Haun, Barbara Kollerits, Florian Kronenberg, Markus Ketteler, Christoph Wanner
INTRODUCTION: Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. METHODS: We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD)...
2017: PloS One
https://www.readbyqxmd.com/read/28194484/perturbations-of-the-anti-ageing-hormone-klotho-in-patients-with-type-1-diabetes-and-microalbuminuria
#3
Giuseppe Maltese, Nikolaos Fountoulakis, Richard C Siow, Luigi Gnudi, Janaka Karalliedde
AIMS/HYPOTHESIS: Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown. METHODS: In a cross-sectional single-centre study we evaluated the levels of circulating serum soluble Klotho in 33 participants with type 1 diabetes and a history of microalbuminuria (receiving renin-angiotensin system [RAS] inhibitors) and 45 participants with type 1 diabetes without a history of microalbuminuria (not receiving RAS or other antihypertensive drugs)...
February 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/28183805/klotho-expression-in-long-bones-regulates-fgf23-production-during-renal-failure
#4
Jovana Kaludjerovic, Hirotaka Komaba, Tadatoshi Sato, Reinhold G Erben, Roland Baron, Hannes Olauson, Tobias E Larsson, Beate Lanske
Circulating levels of bone-derived fibroblast growth factor 23 (FGF23) increase early during acute and chronic kidney disease and are associated with adverse outcomes. Membrane-bound Klotho acts as a permissive coreceptor for FGF23, and its expression was recently found in osteoblasts/osteocytes. We hypothesized that Klotho in bone cells is part of an autocrine feedback loop that regulates FGF23 expression during renal failure. Thus, we induced renal failure in mice with targeted deletion of Klotho in long bones...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28183357/proangiogenic-effects-of-soluble-%C3%AE-klotho-on-systemic-sclerosis-dermal-microvascular-endothelial-cells
#5
Celestina Mazzotta, Mirko Manetti, Irene Rosa, Eloisa Romano, Jelena Blagojevic, Silvia Bellando-Randone, Cosimo Bruni, Gemma Lepri, Serena Guiducci, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
BACKGROUND: Systemic sclerosis (SSc) is characterized by endothelial cell (EC) apoptosis, impaired angiogenesis and peripheral microvasculopathy. Soluble α-Klotho (sKl) is a pleiotropic molecule with multiple effects on ECs, including antioxidant and vasculoprotective activities. On the EC surface, sKl interacts with vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) and transient receptor potential canonical-1 (TRPC-1) cation channel to control EC homeostasis. Here, we investigated whether sKl might act as a protective factor to improve angiogenesis in dermal microvascular endothelial cells (MVECs) from SSc patients (SSc-MVECs)...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28157067/serum-klotho-levels-in-acute-kidney-injury%C3%A2
#6
Eric Seibert, Daniel Radler, Christof Ulrich, Sylvia Hanika, Roman Fiedler, Matthias Girndt
AIMS: Klotho is a co-receptor for FGF-23 and key regulator of phosphate excretion. Soluble klotho modulates ion-channel expression and growth factor sensitivity. In chronic kidney disease (CKD), impaired klotho expression has been demonstrated. Likewise, reduced soluble klotho levels in serum and urine have been established in rodents in experimental acute kidney injury (AKI). In contrast, no data on soluble serum klotho levels in human AKI has been presented to date. MATERIAL AND METHODS: A cross-sectional case-control study of klotho serum levels in 30 subjects with AKI and 126 control subjects with kidney functions ranging from normal to end-stage renal disease (ESRD)...
February 3, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28153033/klotho-an-anti-aging-gene-acts-as-a-tumor-suppressor-and-inhibitor-of-igf-1r-signaling-in-diffuse-large-b-cell-lymphoma
#7
Xiangxiang Zhou, Xiaosheng Fang, Yujie Jiang, Lingyun Geng, Xinyu Li, Ying Li, Kang Lu, Peipei Li, Xiao Lv, Xin Wang
BACKGROUND: Klotho, is a transmembrane protein, performs as a circulating hormone and upstream modulator of the insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor (FGF), and Wnt signaling pathways. These pathways are involved in the development and progression of B cell lymphoma. We aimed to explore the expression pattern and functional mechanism of Klotho in diffuse large B cell lymphoma (DLBCL). METHODS: Immunohistochemistry (IHC) and western blotting were performed to detect the expression level of Klotho in DLBCL patients and cell lines...
February 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28152512/klotho-suppresses-the-inflammatory-responses-and-ameliorates-cardiac-dysfunction-in-aging-endotoxemic-mice
#8
Haipeng Hui, Yufeng Zhai, Lihua Ao, Joseph C Cleveland, Hongbin Liu, David A Fullerton, Xianzhong Meng
BACKGROUND: Aging augments endotoxemic cardiac dysfunction, but the mechanism remains unclear. Anti-aging protein Klotho has been found to modulate tissue inflammatory responses. We tested the hypothesis that a reduced Klotho level in aging heart plays a role in the augmented endotoxemic cardiac dysfunction. MATERIALS AND METHODS: Endotoxin (0.5 mg/kg, iv) was injected to adults (4-6 months) and aging (18-20 months) C57BL/6 mice. Recombinant Klotho (10 μg/kg, iv) was administered to a group of aging mice after endotoxin injection...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28134398/-new-biomarkers-of-ckd-mbd
#9
Marzia Pasquali, Lida Tartaglione, Silverio Rotondi
Chronic kidney failure involves abnormalities of mineral metabolism, skeletal and of cardiovascular system (so called CKD - MBD) that have a major impact on the survival of renal patient. Increasingly complex pathophysiological mechanisms have been discovered in recent years with evidence of new molecules involved in the development of CKD - MBD. Besides the classical PTH / Vitamin D axis, the most recent discovery of a new FGF23 / Klotho axis has expanded knowledge on the mechanisms of mineral homeostasis but also on the more complex mechanisms of cellular aging, vascular calcification and cardiac remodeling...
November 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28131398/recombinant-%C3%AE-klotho-may-be-prophylactic-and-therapeutic-for-acute-to-chronic-kidney-disease-progression-and-uremic-cardiomyopathy
#10
Ming Chang Hu, Mingjun Shi, Nancy Gillings, Brianna Flores, Masaya Takahashi, Makoto Kuro-O, Orson W Moe
α-Klotho is highly expressed in the kidney, and its extracellular domain is cleaved and released into the circulation. Chronic kidney disease (CKD) is a state of α-Klotho deficiency, which exerts multiple negative systemic effects on numerous organs including the cardiovascular system. Since acute kidney injury (AKI) greatly escalates the risk of CKD development, we explored the effect of α-Klotho on prevention and treatment on post-AKI to CKD progression and cardiovascular disease. Therein, ischemia reperfusion injury-induced AKI was followed by early administration of recombinant α-Klotho or vehicle starting one day and continued for four days after kidney injury (CKD prevention protocol)...
January 25, 2017: Kidney International
https://www.readbyqxmd.com/read/28131132/fibroblast-growth-factor-23-mediated-bone-disease
#11
REVIEW
Anda R Gonciulea, Suzanne M Jan De Beur
Fibroblast growth factor 23 (FGF23) is an important regulator of phosphate and vitamin D metabolism and its excessive or insufficient production leads to a wide variety of skeletal disorders. This article reviews the FGF23-α-Klotho signaling pathway, highlighting the latest developments in FGF23 regulation and action, and describes the disorders associated with FGF23 excess or deficiency.
March 2017: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/28130792/klotho-attenuated-antibody-mediated-porcine-endothelial-cell-activation-and-injury
#12
Lu Liu, Hanchao Gao, Chungu Hong, Chen He, Dengke Pan, Yifan Dai, Hidetaka Hara, David K C Cooper, Zesong Li, Zhiming Cai, Lisha Mou
Long-term success in pig-to-primate xenotransplantation is currently hampered by acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and injury. Klotho has anti-apoptotic, anti-inflammatory effects on EC and protects EC against reactive oxygen species, rendering klotho a promising molecule to control AVR. In this study, porcine ECs were pre-incubated with klotho and then exposed to xenoreactive antibodies and complement. Real-time PCR revealed that klotho suppressed antibody-induced pro-inflammatory gene expression of VCAM-1 and IL-1α...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28130714/the-effect-of-nephrectomy-on-klotho-fgf-23-and-bone-metabolism
#13
Katarzyna Kakareko, Alicja Rydzewska-Rosolowska, Szymon Brzosko, Joanna Gozdzikiewicz-Lapinska, Ewa Koc-Zorawska, Pawel Samocik, Robert Kozlowski, Michal Mysliwiec, Beata Naumnik, Tomasz Hryszko
BACKGROUND: Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels...
January 27, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28129785/human-umbilical-cord-derived-mesenchymal-stromal-cells-protect-against-premature-renal-senescence-resulting-from-oxidative-stress-in-rats-with-acute-kidney-injury
#14
Camila Eleuterio Rodrigues, José Manuel Condor Capcha, Ana Carolina de Bragança, Talita Rojas Sanches, Priscila Queiroz Gouveia, Patrícia Aparecida Ferreira de Oliveira, Denise Maria Avancini Costa Malheiros, Rildo Aparecido Volpini, Mirela Aparecida Rodrigues Santinho, Bárbara Amélia Aparecida Santana, Rodrigo do Tocantins Calado, Irene de Lourdes Noronha, Lúcia Andrade
BACKGROUND: Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats...
January 28, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28122194/histochemical-examination-on-periodontal-tissues-of-klotho-deficient-mice-fed-with-phosphate-insufficient-diet
#15
Kumiko Hikone, Tomoka Hasegawa, Erika Tsuchiya, Hiromi Hongo, Muneteru Sasaki, Tomomaya Yamamoto, Ai Kudo, Kimimitsu Oda, Mai Haraguchi, Paulo Henrique Luiz de Freitas, Minqi Li, Junichiro Iida, Norio Amizuka
To elucidate which of elevated serum concentration of inorganic phosphate (Pi) or disrupted signaling linked to αklotho/fibroblast growth factor 23 (FGF23) is a predominant regulator for senescence-related degeneration seen in αKlotho-deficient mice, we have examined histological alteration of the periodontal tissues in the mandibular interalveolar septum of αKlotho-deficient mice fed with Pi-insufficient diet. We prepared six groups of mice: wild-type, kl/kl, and αKlotho(-/-) mice with normal diet or low-Pi diet...
January 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28120476/mineral-adaptations-following-kidney-transplantation
#16
Sven-Jean Tan, Amy Crosthwaite, David Langsford, Varuni Obeysekere, Frank L Ierino, Matthew A Roberts, Peter D Hughes, Tim D Hewitson, Karen M Dwyer, Nigel D Toussaint
BACKGROUND: Klotho is predominantly expressed in the kidney and reported to have anti-oxidant and anti-fibrotic properties. Soluble-Klotho (sKl), the circulating protein cleaved from membrane-bound Klotho, is reduced significantly with kidney disease and inversely associated with mortality. sKl has not been thoroughly evaluated prospectively after kidney transplantation. METHODS: Incident kidney transplant recipients (KTRs) were prospectively evaluated pre-transplantation, 1-week, 12-weeks and 52-weeks post-transplantation...
January 25, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28119179/the-chronic-kidney-disease-mineral-bone-disorder-ckd-mbd-advances-in-pathophysiology
#17
REVIEW
Keith A Hruska, Toshifumi Sugatani, Olga Agapova, Yifu Fang
The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. New advances in the causes of the CKD-MBD are discussed in this review. They demonstrate that repair and disease processes in the kidneys release factors to the circulation that cause the systemic complications of CKD. The discovery of WNT inhibitors, especially Dickkopf 1 (Dkk1), produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical...
January 21, 2017: Bone
https://www.readbyqxmd.com/read/28116736/association-study-of-klotho-gene-polymorphism-with-calcium-oxalate-stones-in-the-uyghur-population-of-xinjiang-china
#18
Abdusamat Ali, Halmurat Tursun, Alim Talat, Akpar Abla, Erpan Muhtar, Tao Zhang, Murat Mahmut
PURPOSE: The aim of the present study was to investigate the correlation between Klotho gene polymorphisms andcalcium oxalate stones in Xinjiang Uyghur people. MATERIALS AND METHODS: We compared 128 patients with calcium oxalate stones (case group) and 94 healthypeople (control group), detected the genotype and allele distributions of single-nucleotide polymorphisms (SNPs)of the Klotho gene (rs3752472, rs650439, and rs1207568) by reverse transcription polymerase chain reaction...
January 18, 2017: Urology Journal
https://www.readbyqxmd.com/read/28115282/potential-application-of-klotho-in-human-chronic-kidney-disease
#19
REVIEW
Javier A Neyra, Ming Chang Hu
The extracellular domain of transmembrane alpha-Klotho (αKlotho, hereinafter simply called Klotho) is cleaved by secretases and released into the circulation as soluble Klotho. Soluble Klotho in the circulation starts to decline early in chronic kidney disease (CKD) stage 2 and urinary Klotho possibly even earlier in CKD stage 1. Therefore soluble Klotho could serve as an early and sensitive marker of kidney function decline. Moreover, preclinical animal data support Klotho deficiency is not just merely a biomarker, but a pathogenic factor for CKD progression and extrarenal CKD complications including cardiovascular disease and disturbed mineral metabolism...
January 20, 2017: Bone
https://www.readbyqxmd.com/read/28112974/assessment-of-the-anti-aging-klotho-protein-in-patients-with-copd-undergoing-pulmonary-rehabilitation
#20
Judit Pako, Imre Barta, Zsuzsanna Balogh, Maria Kerti, Orsolya Drozdovszky, Andras Bikov, Balazs Antus, Ildiko Horvath, Janos Varga
Chronic obstructive pulmonary disease (COPD) is associated with the accelerated aging of the lung. The protein klotho has been implicated in longevity, and there is some evidence that it might be involved in the pathomechanism of chronic respiratory diseases. Therefore, we aimed to examine whether the clinical condition of COPD patients is reflected in plasma klotho concentration. As plasma concentration of the protein is modulated by physiological factors that are generally improved during pulmonary rehabilitation, we hypothesized that a complex rehabilitation program may alter plasma klotho concentration...
January 23, 2017: COPD
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