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Klotho

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https://www.readbyqxmd.com/read/28104822/association-between-soluble-klotho-and-change-in-kidney-function-the-health-aging-and-body-composition-study
#1
David A Drew, Ronit Katz, Stephen Kritchevsky, Joachim Ix, Michael Shlipak, Orlando M Gutiérrez, Anne Newman, Andy Hoofnagle, Linda Fried, Richard D Semba, Mark Sarnak
CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble α-klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1...
January 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28096966/microrna-297a-regulates-vascular-calcification-by-targeting-fibroblast-growth-factor-23
#2
Shouhua Zheng, Shuijun Zhang, Yan Song, Wenzhi Guo, Wenlong Zhai, Xinguang Qiu, Jianhua Li
OBJECTIVES: Vascular calcification is one the major characteristics in patients with various types of chronic inflammatory disorders. MiRNAs have been shown to be involved in many normal biological functions as well as diseases; however, their role in vascular calcification has not received much attention. MATERIALS AND METHODS: In the current study, we built a vascular calcification rat model using vitamin D3 plus nicotine and analyzed miRNA expression profile by miRNA chip assay...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28095739/expression-and-localization-of-fibroblast-growth-factor-fgf-23-and-klotho-in-the-spleen-its-physiological-and-functional-implications
#3
Yuri Nakashima, Toru Mima, Mitsuru Yashiro, Tomohiro Sonou, Masaki Ohya, Asuka Masumoto, Shintaro Yamanaka, Daisuke Koreeda, Koichi Tatsuta, Yoshiyuki Hanba, Mari Moribata, Shigeo Negi, Takashi Shigematsu
The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220(+) CD21/CD35(+) CD1d(+) CD43(-) marginal zone B cells...
January 18, 2017: Growth Factors
https://www.readbyqxmd.com/read/28095050/the-expressions-of-klotho-family-genes-in-human-ocular-tissues-and-in-anterior-lens-capsules-of-age-related-cataract
#4
Yu Zhang, Liya Wang, Zhong Wu, Xiaolin Yu, Xiaofeng Du, Xiaohua Li
PURPOSE: Klotho genes are expressed in limited tissues and have been found to be a pathogenic factor of age-related diseases in mammals, but their expressions and functions in human eyes are yet to be defined. This study was performed to investigate the expression of Klotho family genes in human ocular tissues and anterior lens capsules of age-related cataract. METHODS: Individual tissues were isolated from human eyeballs collected from Henan Eye Bank. Human anterior lens capsules were collected from cortical cataract patients during phacoemulsification with the informed consent...
January 17, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#5
Katie C Coate, Genaro Hernandez, Curtis A Thorne, Shengyi Sun, Thao D V Le, Kevin Vale, Steven A Kliewer, David J Mangelsdorf
The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho. Mice lacking FGF21 accumulate zymogen granules and are susceptible to pancreatic ER stress, an effect that is reversed by administration of recombinant FGF21...
December 27, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28076518/serum-klotho-but-not-haplotypes-associate-with-the-post-myocardial-infarction-status-of-older-adults
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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