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https://www.readbyqxmd.com/read/28337713/the-potential-role-of-fibroblast-growth-factor-21-in-lipid-metabolism-and-hypertension
#1
REVIEW
Zhe Huang, Aimin Xu, Bernard M Y Cheung
Fibroblast growth factor (FGF) 21 belongs to the FGF superfamily that is involved in cell proliferation and differentiation, neural development, angiogenesis, and metabolism. FGF21 requires β-Klotho as a co-receptor. Tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas express FGF21. Starvation increases hepatic expression of FGF21, which then acts centrally to increase hepatic gluconeogenesis. FGF21 also increases fatty acid oxidation. This may be relevant in cold exposure, when expression of FGF21 is induced...
April 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28336912/fgf21-regulates-t-cell-development-in-the-neonatal-and-juvenile-thymus
#2
Yoshiaki Nakayama, Yuki Masuda, Hiroya Ohta, Tomohiro Tanaka, Miwa Washida, Yo-Ichi Nabeshima, Ayumi Miyake, Nobuyuki Itoh, Morichika Konishi
We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in the thymus as well as in the liver. In line with this expression profile, Fgf21 was recently reported to protect against ageing-related thymic senescence by improving the function of thymic epithelial cells (TECs). However, the function of Fgf21 in the juvenile thymus remained to be elucidated. We investigated the physiological roles of Fgf21 in the juvenile thymus and found that young Fgf21 knockout mice, but not β-Klotho knockout mice nor adult Fgf21 knockout mice, showed a significant reduction in the percentage of single-positive CD4(+) and CD8(+) thymocytes without obvious alteration in TECs...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#3
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332126/klotho-suppresses-high-phosphate-induced-osteogenic-responses-in-human-aortic-valve-interstitial-cells-through-inhibition-of-sox9
#4
Fei Li, Qingzhou Yao, Lihua Ao, Joseph C Cleveland, Nianguo Dong, David A Fullerton, Xianzhong Meng
Elevated level of blood phosphate (Pi) associated with chronic kidney disease (CKD) is a risk factor of aortic valve calcification. Aortic valve interstitial cells (AVICs) display osteogenic responses to high Pi although the underlying mechanism is incompletely understood. Sox9 is a pro-chondrogenic factor and may play a role in ectopic tissue calcification. Circulating and kidney levels of Klotho are reduced in patients with CKD. We hypothesized that Sox9 mediates high Pi-induced osteogenic responses in human AVICs and that Klotho inhibits the responses...
March 22, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28329753/benefits-of-high-intensity-exercise-training-to-patients-with-chronic-obstructive-pulmonary-disease-a-controlled-study
#5
Tobias Boeselt, Christoph Nell, Lea Lütteken, Katharina Kehr, Janine Koepke, Sandra Apelt, Martina Veith, Björn Beutel, Marc Spielmanns, Timm Greulich, Claus F Vogelmeier, Klaus Kenn, Sabina Janciauskiene, Peter Alter, A Rembert Koczulla
BACKGROUND: Various exercise training programs are used for patients with chronic obstructive pulmonary disease (COPD) of different severity. OBJECTIVES: To investigate the impact of individualized high-intensity training on exercise capacity with COPD. METHODS: A total of 49 patients agreed to participate. Of these, 31 were assigned to the training group and 18 served as controls. The training group exercised twice a week for 90 min with consecutively increasing loads...
March 23, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28324011/a-novel-fc-fgf21-with-improved-resistance-to-proteolysis-increased-affinity-towards-%C3%AE-klotho-and-enhanced-efficacy-in-mice-and-cynomolgus-monkeys
#6
Shanaka Stanislaus, Randy Hecht, Junming Yie, Todd Hager, Michael Hall, Chris Spahr, Wei Wang, Jennifer Weiszmann, Yang Li, Liying Deng, Dwight Winters, Stephen Smith, Lei Zhou, Yuesheng Li, Murielle M Véniant, Jing Xu
FGF21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to β-Klotho. We demonstrate, by introducing one additional mutation located at the C-terminus of FGF21 (A180E) that the new molecule, Fc-FGF21(RGE), has gained many improved attributes...
January 26, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323144/tissue-expression-and-source-of-circulating-%C3%AE-klotho
#7
REVIEW
Hannes Olauson, Rik Mencke, Jan-Luuk Hillebrands, Tobias E Larsson
αKlotho (Klotho), a type I transmembrane protein and a coreceptor for Fibroblast growth factor-23, was initially thought to be expressed only in a limited number of tissues, most importantly the kidney, parathyroid gland and choroid plexus. Emerging data may suggest a more ubiquitous Klotho expression pattern which has prompted reevaluation of the restricted Klotho paradigm. Herein we systematically review the evidence for Klotho expression in various tissues and cell types in humans and other mammals, and discuss potential reasons behind existing conflicting data...
March 17, 2017: Bone
https://www.readbyqxmd.com/read/28323064/the-relevance-of-%C3%AE-klotho-to-the-central-nervous-system-some-key-questions
#8
REVIEW
Marina Minto Lopes-Cararo, Caio Henrique Yokoyama Mazucanti, Cristoforo Scavone, Elisa Mitiko Kawamoto, Daniel Charles Berwick
α-Klotho is well described as an anti-aging protein, with critical roles in kidney function as a transmembrane co-receptor for FGF23, and as a soluble factor in serum. α-Klotho is also expressed in the choroid plexus, where it is released into the cerebrospinal fluid. Nonetheless, α-Klotho is also expressed in the brain parenchyma. Accumulating evidence indicates that this pool of α-Klotho, which we define as brain α-Klotho, may play important roles as a neuroprotective factor and in promoting myelination, thereby supporting healthy brain aging...
March 18, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28320994/a-nomogram-to-predict-contrast-induced-nephropathy-in-patients-undergoing-percutaneous-coronary-intervention
#9
Xun Hu, Xiao-Dong Zhuang, Yi Li, Fei-Fei Li, Yue Guo, Zhi-Min Du, Xin-Xue Liao
Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury (AKI). Emerging evidence has revealed that soluble klotho (sklotho) could be a novel biomarker for early AKI diagnosis. The aims of this study were to assess the predictive role of sklotho for CIN and to develop a prediction nomogram in patients undergoing percutaneous coronary intervention (PCI). This study is registered on Clinicaltrials.gov (NCT 02650336).Patients aged 18 years or older undergoing planned PCI were prospectively recruited between May 2014 and July 2015...
March 21, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28315683/klotho-ameliorates-cyclosporine-a-induced-nephropathy-via-pdlim2-nf-kb-p65-signaling-pathway
#10
Meihua Jin, Pengfei Lv, Guanyu Chen, Peng Wang, Zhongfu Zuo, Lili Ren, Jing Bi, Chul-Woo Yang, Xifan Mei, Donghe Han
Klotho, an antiaging protein, can extend the lifespan and modulate cellular responses to inflammation and oxidative stress which can ameliorate chronic kidney diseases (CKD). To investigate the molecular mechanism of Klotho on inflammation in cyclosporine A (CsA) induced nephropathy, the mice were transfected with adenovirus mediated Klotho gene and treated with cyclosporine A (CsA; 30 mg/kg/day) for 4 weeks. Also, primary human renal proximal tubule epithelial cells (RPTECs) were treated with soluble Klotho protein and LPS...
March 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314576/trpc6-and-kidney-disease-sclerosing-more-than-just-glomeruli
#11
Johannes Schlondorff
Fibrosis is a common response to injury but can also perpetuate tissue dysfunction. Transient receptor potential C6 (TRPC6) is implicated in cardiac and skin healing via regulation of myofibroblast differentiation. Wu et al. now demonstrate a role for TRPC6 in renal fibrosis, via a mechanism that also relies on TRPC3 and is antagonized by soluble klotho. Modulation of TRPC3/6 activity may provide a means of dampening the fibrotic response involved in chronic kidney disease progression.
April 2017: Kidney International
https://www.readbyqxmd.com/read/28303350/immunohistochemical-evaluation-of-klotho-and-dna-methyltransferase-3a-in-oral-squamous-cell-carcinomas
#12
Bhoj Raj Adhikari, Osamu Uehara, Hirofumi Matsuoka, Rie Takai, Fumiya Harada, Masafumi Utsunomiya, Takatoshi Chujo, Tetsuro Morikawa, Mamata Shakya, Koki Yoshida, Jun Sato, Toshiya Arakawa, Michiko Nishimura, Hiroki Nagayasu, Itsuo Chiba, Yoshihiro Abiko
Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma...
March 16, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28294047/klotho-fgf23-cardiovascular-disease-and-vascular-calcification-black-or-white
#13
Giuseppe Cianciolo, Andrea Galassi, Irene Capelli, Roberto Schillaci, Gaetano La Manna, Mario Cozzolino
Patients affected by Chronic Kidney Disease and Mineral Bone Disorder (CKD-MBD) have a high risk of cardiovascular (CV) mortality that is poorly explained by traditional risk factors. The newest medical treatments for CKD-MBD have been associated with encouraging, but still inconsistent, improvement in CV disease complications and patient survival. A better understanding of the biomarkers and mechanisms of left ventricular hypertrophy (LVH), atherosclerosis, and vascular calcification (VC) may help with diagnosis and treatment of the organ damage that occurs secondary to CKD-MBD, thus improving survival...
March 9, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28288230/-somatotropic-axis-and-molecular-markers-of-mineral-metabolism-in-children-undergoing-chronic-peritoneal-dialysis
#14
María Luisa Ceballos Osorio, Francisco Cano Schuffeneger
Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. OBJECTIVES: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. PATIENTS AND METHOD: A longitudinal 12-month follow-up in prepuberal PD children...
February 2017: Revista Chilena de Pediatría
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#15
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not appreciably established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28276159/comparative-proteome-analysis-of-wild-type-and-klotho-knockout-mouse-kidneys-using-a-combination-of-maldi-ims-and-lc-ms-ms
#16
Yoko Fujino, Tomoko Minamizaki, Ikue Hayashi, Asako Kawakami, Takaaki Miyaji, Kaoru Sakurai, Hirotaka Yoshioka, Katsuyuki Kozai, Mitsugi Okada, Yuji Yoshiko
PURPOSE: Mutation of the klotho gene in mice elicits a syndrome resembling accelerated human aging. However, there is limited evidence for the role of Klotho in the kidney. We conducted a comparative proteome analysis of wild-type (WT) and Klotho-knockout (kl(-/-) ) mouse kidneys to identify proteins involved in Klotho deficiency. EXPERIMENTAL DESIGN: MALDI-IMS of frozen kidney sections from 7-week-old male WT and kl(-/-) mice was used to determine genotype-specific differences in the MS distribution...
March 8, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28270648/relationship-of-serum-klotho-level-with-ace-gene-polymorphism-in-stable-kidney-allograft-recipients
#17
Maryam Zaare Nahandi, Mohamad Reza Ardalan, Ali Banagozar Mohamadi, Amir Ghorbani Haghjo, Morteza Jabbarpor Bonyadi, Tahere Mohamadian
INTRODUCTION: The kidney is the main source of serum Klotho production. Immunosuppressive agents could affect the kidney in this regard. The effect of the ACE gene polymorphism on Klotho production is a less studied area. This study aimed to assess serum Klotho and ACE gene in a group of stable kidney transplant recipients. MATERIALS AND METHODS: In a cross-sectional study, 30 kidney transplant recipients with stable allograft function and 27 healthy young individuals were assessed for their serum Klotho levels...
March 2017: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/28264799/uremic-solute-indoxyl-sulfate-induced-platelet-hyperactivity-contributes-to-ckd-associated-thrombosis-in-mice
#18
Ke Yang, Changhong Du, Xinmiao Wang, Fengju Li, Yang Xu, Song Wang, Shilei Chen, Fang Chen, Mingqiang Shen, Mo Chen, Mengjia Hu, Ting He, Yongping Su, Junping Wang, Jinghong Zhao
Thrombosis is a common complication of chronic kidney disease (CKD), but the causes and mechanisms of CKD-associated thrombosis are not well clarified. Here, we show that platelet activity is remarkably enhanced in CKD mice, with increase of serum indoxyl sulfate (IS), a typical uremic toxin which cannot be effectively cleared by routine dialysis. Ex vivo and in vitro experiments reveal that IS displays a distinct ability to enhance platelet activities, including elevated response to collagen and thrombin, increases in platelet-derived microparticles and platelet-monocyte aggregates...
March 6, 2017: Blood
https://www.readbyqxmd.com/read/28259911/reduced-klotho-expression-contributes-to-poor-survival-rates-in-human-patients-with-ovarian-cancer-and-overexpression-of-klotho-inhibits-the-progression-of-ovarian-cancer-partly-via-the-inhibition-of-systemic-inflammation-in-nude-mice
#19
Youliang Yan, Yifeng Wang, Yi Xiong, Xiufeng Lin, Ping Zhou, Zhiying Chen
Klotho is a recently discovered anti‑aging gene, which has been reported as a tumor suppressor in numerous human malignancies; however, the role of Klotho in human ovarian cancer remains to be elucidated. The aim of the present study was to detect the expression of Klotho and evaluate its association with the progression of human ovarian cancer. A clinical follow‑up study of 120 patients with ovarian cancer and 78 normal controls was conducted. The expression levels of Klotho were determined by western blotting and immunohistochemistry...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255001/physiology-and-pathophysiology-of-the-intrarenal-renin-angiotensin-system-an-update
#20
Tianxin Yang, Chuanming Xu
The renin-angiotensin system (RAS) has a pivotal role in the maintenance of extracellular volume homeostasis and blood pressure through complex mechanisms. Apart from the well known systemic RAS, occurrence of a local RAS has been documented in multiple tissues, including the kidney. A large body of recent evidence from pharmacologic and genetic studies, particularly those using various transgenic approaches to manipulate intrarenal levels of RAS components, has established the important role of intrarenal RAS in hypertension...
March 2, 2017: Journal of the American Society of Nephrology: JASN
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