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Hong-Jing Zhou, Chen-Ye Zeng, Ting-Ting Yang, Fang-Yi Long, Xi Kuang, Jun-Rong Du
AIMS: Oxidative stress caused by aging aggravates neuropathological changes and cognitive deficits. Klotho, an anti-aging protein, shows an anti-oxidative effect. The aims of the present study were to determine the potential therapeutic effect of klotho in aging-related neuropathological changes and memory impairments in senescence-accelerated mouse prone-8 (SAMP8) mice, and identify the potential mechanism of these neuroprotective effects. MATERIALS AND METHODS: A lentiviral was used to deliver and sustain the expression of klotho...
March 12, 2018: Life Sciences
Mohammad Sajad Emami Aleagha, Mohammad Hossein Harirchian, Shahram Lavasani, Mohammad Javan, Abdolamir Allameh
Recently, we reported a positive correlation between Klotho, as an anti-aging protein, and the total antioxidant capacity (TAC) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, there is no information about the Klotho and TAC changes within the central nervous system (CNS). Thus, the current study aimed to employ an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice using MOG35-55 peptide to examine the relationship between Klotho and TAC within the CNS. To this end, the brain and spinal cord were obtained at the onset and peak stages of EAE as well as non-EAE mice (sham/control groups)...
March 14, 2018: Journal of Molecular Neuroscience: MN
A M Rodrigues, R S Serralha, C Farias, G R Punaro, M J S Fernandes, Elisa Mieko Suemitsu Higa
Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X7 ), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X7 and klotho in several stages of diabetes in rats...
March 14, 2018: Purinergic Signalling
Nikolaos Fountoulakis, Giuseppe Maltese, Luigi Gnudi, Janaka Karalliedde
Context and Objective: Soluble Klotho (sKlotho) is a circulating hormone with cardiovascular-renal protective effects. Whether sKlotho predicts estimated glomerular filtration rate (eGFR) decline in type 2 diabetes mellitus (T2DM) patients with relatively preserved renal function is unknown. Design, setting, participants and measurements: Single-centre observational follow-up study of 101 patients with T2DM and eGFR >45 ml/min, [91% on renin angiotensin system (RAS) blockade] followed for a median (range) of 9 (2-13) years...
March 2, 2018: Journal of Clinical Endocrinology and Metabolism
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
Xinxin Chen, Huan Tong, Yu Chen, Chaosheng Chen, Jingjing Ye, Qingfei Mo, Guangju Zhao, Guangliang Hong, Chenfei Zheng, Zhongqiu Lu
Background: The role of Klotho (KL) in sepsis-induced acute kidney injury (AKI) and the potential relationship between KL and autophagy in septic AKI were investigated. Materials and methods: A murine model of sepsis-induced AKI was established by cecal ligation and puncture (CLP). Mice undergoing CLP and immortalized proximal tubular epithelial human HK-2 cells that were exposed to lipopolysaccharide (LPS) were treated with recombinant KL, autophagy stimulator rapamycin (Rap), and autophagy suppressor 3-methyladenine (3-MA)...
2018: OncoTargets and Therapy
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...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Ganesh Pathare, Manuel Anderegg, Giuseppe Albano, Florian Lang, Daniel G Fuster
Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH)2 D3 . It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect further in a model of mild hypovolemia, we studied mice lacking the thiazide sensitive NaCl cotransporter (NCC). Our data indicate that NCC knockout mice (KO) have significantly higher FGF23, PTH and aldosterone concentrations than corresponding wild type (WT) mice...
February 26, 2018: Scientific Reports
Yu-Chen Shi, Wei-Wei Lu, Yue-Long Hou, Kun Fu, Feng Gan, Shu-Juan Cheng, Shao-Ping Wang, Yong-Fen Qi, Jing-Hua Liu
Background: Chronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats...
March 5, 2018: Chinese Medical Journal
Sally Yu Shi, Ya-Wen Lu, Zhi Liu, Jennitte Stevens, Christopher M Murawsky, Vicki Wilson, Zhonghua Hu, William G Richards, Mark Leo Michaels, Jun Zhang, Wei Yan, Yang Li
Bispecific antibodies have become important formats for therapeutic discovery. They allow for potential synergy by simultaneously engaging two separate targets and enable new functions that are not possible to achieve by using a combination of two monospecific antibodies. Antagonistic antibodies dominate drug discovery today, but only a limited number of agonistic antibodies (i.e. those that activate receptor signaling) have been described. For receptors formed by two components, engaging both of these components simultaneously may be required for agonistic signaling...
February 26, 2018: Journal of Biological Chemistry
Christian Lerch, Rukshana Shroff, Mandy Wan, Lesley Rees, Helen Aitkenhead, Ipek Kaplan Bulut, Daniela Thurn, Aysun Karabay Bayazit, Anna Niemirska, Nur Canpolat, Ali Duzova, Karolis Azukaitis, Ebru Yilmaz, Fatos Yalcinkaya, Jerome Harambat, Aysel Kiyak, Harika Alpay, Sandra Habbig, Ariane Zaloszyc, Oguz Soylemezoglu, Cengiz Candan, Alejandra Rosales, Anette Melk, Uwe Querfeld, Maren Leifheit-Nestler, Anja Sander, Franz Schaefer, Dieter Haffner
Background: We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD). Methods: In all, 80 vitamin D-deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1...
February 21, 2018: Nephrology, Dialysis, Transplantation
Yanmei Zhou, Yifang Kuang, Jianhua Zhou
AIM: This study aimed to investigate the effect and mechanism of Klotho in lipopolysaccharide (LPS)-induced inflammation injury in HK-2 cells. METHODS: We established LPS-induced inflammation injury model in HK-2 cells. The LPS-induced HK-2 cells were transfected with pc-Klotho, pcDNA3.1, siKlotho or siNC. Cell viability, apoptosis and reactive oxygen species (ROS) level were detected by MTT assay, Annexin V-FITC/PI Apoptosis Detection kit and 2,7-dichlorofluorescein diacetate, respectively...
April 1, 2017: Die Pharmazie
Hongda Liang, Kun Yang, Miaomiao Xin, Xiangping Liu, Lei Zhao, Bin Liu, Jibo Wang
AIMS: Lupus nephritis is a frequent and serious complication of systemic lupus erythematosus (SLE). Therefore, better understanding regarding the underlying mechanism of renal tubular injury induced by SLE, is beneficial to develop different therapeutic strategies for lupus nephritis. The study aimed to investigate the role of miR-130a against lipopolysaccharide-induced glomerular cell injury. METHODS: HK-2 cells (human renal proximal tubule cells) were used for detecting miR-130a levels...
August 1, 2017: Die Pharmazie
Haijun Liu, Xiuhua Xie, Xiuqin Yang, Yanguo Li, Ying Wang, Dongmei Xu
MiR-136 acts as a tumor suppressor by promoting cell apoptosis and downregulating Bcl-2 in glioma cells. Hence, an attempt has been made to evaluate the role of miR-136 in regulation of inflammatory damage in HK-2 cells. HK-2 cells were cultured and assessed for viability. The cells were then transfected with miR-136 mimic, si- miR-136, si-Klotho, and NC. Dual luciferase test was performed to confirm the target of miR-136 which was assumed to be Klotho. Cell viability, apoptosis, expressions of inflammatory cytokines like TNF-α, IL-1β, IL-6 and IL-8 were assessed in HK-2 cells with overexpressing miR-136 or with knocked down miR-136 activities, following exposure to LPS...
May 1, 2017: Die Pharmazie
Jianguo Fan, Joshua Lerner, M Keith Wyatt, Phillip Cai, Katherine Peterson, Lijin Dong, Graeme Wistow
KLPH/lctl belongs to the Klotho family of proteins. Expressed sequence tag analyses unexpectedly revealed that KLPH is highly expressed in the eye lens while northern blots showed that expression is much higher in the eye than in other tissues. In situ hybridization in mouse localized mRNA to the lens, particularly in the equatorial epithelium. Immunofluorescence detected KLPH in lens epithelial cells with highest levels in the germinative/differentiation zone. The gene for KLPH in mouse was deleted by homologous recombination...
February 6, 2018: Experimental Eye Research
Maren Leifheit-Nestler, Felix Kirchhoff, Julia Nespor, Beatrice Richter, Birga Soetje, Michael Klintschar, Joerg Heineke, Dieter Haffner
Background: Fibroblast growth factor 23 (FGF23) is discussed as a new biomarker of cardiac hypertrophy and mortality in patients with and without chronic kidney disease (CKD). We previously demonstrated that FGF23 is expressed by cardiac myocytes, enhanced in CKD and induces cardiac hypertrophy via activation of FGF receptor 4 independent of its co-receptor klotho. The impact of FGF23 on cardiac fibrosis is largely unknown. Methods: By conducting a retrospective case-control study including myocardial autopsy samples from 24 patients with end-stage CKD and in vitro studies in cardiac fibroblasts and myocytes, we investigated the pro-fibrotic properties of FGF23...
February 7, 2018: Nephrology, Dialysis, Transplantation
Beatriz Fernandez-Fernandez, M Concepcion Izquierdo, Lara Valiño-Rivas, Dimitra Nastou, Ana B Sanz, Alberto Ortiz, Maria D Sanchez-Niño
Background: Kidney tubular cells are the main sources of Klotho, a protein with phosphaturic action. Genetic Klotho deficiency causes premature cardiovascular aging in mice. Human chronic kidney disease (CKD) is characterized by acquired Klotho deficiency. Despite the lack of uremic toxin accumulation, Category G1 CKD [(normal glomerular filtration rate (GFR)] is already associated with decreased Klotho and with premature cardiovascular aging. Methods: We have explored whether albuminuria, a criterion to diagnose CKD when GFR is normal, may directly decrease Klotho expression in human CKD, preclinical models and cultured tubular cells...
February 7, 2018: Nephrology, Dialysis, Transplantation
José Alberto Navarro-García, María Fernández-Velasco, Carmen Delgado, Juan F Delgado, Makoto Kuro-O, Luis Miguel Ruilope, Gema Ruiz-Hurtado
Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicate that alterations in phosphate homeostasis could have an even stronger impact on the heart. The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting. Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF-23-Klotho axis have direct pathological consequences for the heart...
February 2, 2018: European Journal of Clinical Investigation
Ralph Schneider, Carolin Steinmetz, Elias Karakas, Detlef K Bartsch, Katja Schlosser
BACKGROUND: After parathyroidectomy (PTX), hungry bone syndrome leads to hypocalcemia due to bone remineralization. The aim of this pilot study was to analyze changes in markers of bone metabolism in patients with secondary hyperparathyroidism (sHPT) after PTX and to correlate these markers with bone pain measured with a validated questionnaire. MATERIALS AND METHODS: All patients who underwent PTX for sHPT between March 2010 and February 2012 at out institution were included in this prospective observational pilot study...
January 23, 2018: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
Lu-Hong Cong, Shi-Yu Du, Yi-Na Wu, Ying Liu, Tao Li, Hui Wang, Gang Li, Jun Duan
We evaluated the effects of Klotho on pulmonary vascular remodeling and cell proliferation and apoptosis in rat models with PM2.5-induced pulmonary arterial hypertension (PAH) via the Wnt signaling pathway. After establishing rat models of PM2.5-induced PAH, these Sprague-Dawley male rats were randomized into control and model groups. Cells extracted from the model rats were sub-categorized into different groups. Activation of Wnt/β-catenin signaling transcription factor was detected by a TOPFlash/FOPFlash assay...
January 30, 2018: Journal of Cellular Biochemistry
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