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Klotho

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https://www.readbyqxmd.com/read/29792935/lp533401-restores-bone-health-in-5-6-nephrectomized-rats-by-a-decrease-of-gut-derived-serotonin-and-regulation-of-serum-phosphate-through-the-inhibition-of-phosphate-co-transporters-expression-in-the-kidneys
#1
Dariusz Pawlak, Beata Znorko, Bartlomiej Kalaska, Tomasz Domaniewski, Radosław Zawadzki, Paweł Lipowicz, Michał Doroszko, Urszula Łebkowska, Piotr Grabowski, Krystyna Pawlak
LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100 mg/kg daily for 8 weeks...
May 21, 2018: Bone
https://www.readbyqxmd.com/read/29782253/-mineral-and-bone-disorders-in-chronic-heart-failure
#2
E V Reznik, I G Nikitin
In many patients, chronic heart failure (CHF) is associated with chronic kidney disease (CKD). Virtually all patients with terminal CKD and many patients with early CKD display various disorders of mineral and bone metabolism (MBM) related with all-cause mortality and high risk of cardiovascular complications. This review addressed disorders of mineral and bone metabolism in patients with CHF, including hypocalcemia, hyperphosphatemia, vitamin D insufficiency/deficiency, secondary hyperparathyroidism, changed levels of FGF23 and Klotho, osteoporosis, osteopenia, their clinical and prognostic significance, and possibilities of their correction...
2018: Kardiologiia
https://www.readbyqxmd.com/read/29780355/therapeutic-interference-with-vascular-calcification-lessons-from-klotho-hypomorphic-mice-and-beyond
#3
REVIEW
Florian Lang, Christina Leibrock, Lisann Pelzl, Meinrad Gawaz, Burkert Pieske, Ioana Alesutan, Jakob Voelkl
Medial vascular calcification, a major pathophysiological process associated with cardiovascular disease and mortality, involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). In chronic kidney disease (CKD), osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification is mainly driven by hyperphosphatemia, resulting from impaired elimination of phosphate by the diseased kidneys. Hyperphosphatemia with subsequent vascular calcification is a hallmark of klotho-hypomorphic mice, which are characterized by rapid development of multiple age-related disorders and early death...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29775618/association-between-klotho-expression-and-malignancies-risk-and-progression-a-meta-analysis
#4
Song Mao, Xiaopeng Wang, Liangxia Wu, Dou Zang, Wenjing Shi
BACKGROUND: We assessed the association between tissue klotho protein expression and the risk and progression of malignancies. METHODS: We searched the electronic databases for the studies regarding the relationship between tissue klotho protein expression and risk/progression of malignancies through January 2018. We calculated the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to evaluate the impact of tissue klotho protein expression on malignancies...
May 17, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29770125/fgf23-actions-on-target-tissues-with-and-without-klotho
#5
REVIEW
Beatrice Richter, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone whose physiologic actions on target tissues are mediated by FGF receptors (FGFR) and klotho, which functions as a co-receptor that increases the binding affinity of FGF23 for FGFRs. By stimulating FGFR/klotho complexes in the kidney and parathyroid gland, FGF23 reduces renal phosphate uptake and secretion of parathyroid hormone, respectively, thereby acting as a key regulator of phosphate metabolism. Recently, it has been shown that FGF23 can also target cell types that lack klotho...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29768278/lower-plasma-klotho-concentrations-are-associated-with-vascular-dementia-but-not-late-onset-alzheimer-s-disease
#6
Gloria Brombo, Francesco Bonetti, Beatrice Ortolani, Mario Luca Morieri, Cristina Bosi, Angelina Passaro, Giovanni B Vigna, Caterina Borgna, Maria Vittoria Arcidicono, Veronica Tisato, Giovanni Zuliani
BACKGROUND: The protein Klotho is involved in biological processes related to longevity, cardiovascular health, and cognition. Serum Klotho levels have been associated with better cognition in animal models; moreover, lower Klotho concentrations in cerebrospinal fluid from subjects with late-onset Alzheimer's disease (LOAD) have been reported. OBJECTIVE: Our study aimed to examine the possible relationship between Klotho plasma concentrations and cognitive status in the elderly...
May 16, 2018: Gerontology
https://www.readbyqxmd.com/read/29767399/a-decreased-soluble-klotho-level-with-normal-egfr-fgf23-serum-phosphate-and-fep-in-an-adpkd-patient-with-enlarged-kidneys-due-to-multiple-cysts
#7
Takahiro Kanai, Kazuhiro Shiizaki, Hiroyuki Betsui, Jun Aoyagi, Takanori Yamagata
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR...
May 16, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29755348/the-fibrin-cleavage-product-b%C3%AE-15-42-channels-endothelial-and-tubular-regeneration-in-the-post-acute-course-during-murine-renal-ischemia-reperfusion-injury
#8
Dania Fischer, Christopher Seifen, Patrick Baer, Michaela Jung, Christina Mertens, Bertram Scheller, Kai Zacharowski, Rainer Hofmann, Thorsten J Maier, Anja Urbschat
Early and adequate restoration of endothelial and tubular renal function is a substantial step during regeneration after ischemia reperfusion (IR) injury, occurring, e.g., in kidney transplantation, renal surgery, and sepsis. While tubular epithelial cell injury has long been of central importance, recent perception includes the renal vascular endothelium. In this regard, the fibrin cleavage product fibrinopeptide Bβ15-42 mitigate IR injury by stabilizing interendothelial junctions through its affinity to VE-cadherin...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29754009/dietary-nitrogen-and-calcium-modulate-cyp27b1-expression-in-young-goats
#9
M R Wilkens, K Elfers, M Schmicke, G Breves, A S Muscher-Banse
In livestock, feeding a reduced nitrogen (N) diet is favored for economic and ecological reasons. Ruminants cope more easily with a reduced N diet than monogastric species. However, changes in mineral homeostasis such as a reduction in 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ) concentrations, calcium (Ca), and IGF1 levels were observed in goats kept on a reduced N diet. The decrease in 1,25-(OH)2 D3 occurred even during a simultaneous reduction in dietary N and Ca, whereas a solitary Ca reduction stimulated 1,25-(OH)2 D3 synthesis...
April 3, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29751971/cardiac-hypertrophy-elevates-serum-levels-of-fibroblast-growth-factor-23
#10
Isao Matsui, Tatsufumi Oka, Yasuo Kusunoki, Daisuke Mori, Nobuhiro Hashimoto, Ayumi Matsumoto, Karin Shimada, Satoshi Yamaguchi, Keiichi Kubota, Sayoko Yonemoto, Tomoaki Higo, Yusuke Sakaguchi, Yoshitsugu Takabatake, Takayuki Hamano, Yoshitaka Isaka
Several experimental studies have shown that fibroblast growth factor 23 (FGF23) induces left ventricular hypertrophy (LVH). However, the opposite directional relationship, namely a potential effect of LVH on FGF23, remains uncertain. Here we evaluated the effects of LVH on FGF23 using cardiomyocyte-specific calcineurin A transgenic mice. At six weeks, these mice showed severe LVH, with elevated levels of serum intact FGF23. FGF23 levels were elevated in cardiomyocytes, but not osteocytes, of the transgenic animals...
May 8, 2018: Kidney International
https://www.readbyqxmd.com/read/29748308/fibroblast-growth-factor-23-and-klotho-contribute-to-airway-inflammation
#11
Stefanie Krick, Alexander Grabner, Nathalie Baumlin, Christopher Yanucil, Scott Helton, Astrid Grosche, Juliette Sailland, Patrick Geraghty, Liliana Viera, Derek W Russell, J Michael Wells, Xin Xu, Amit Gaggar, Jarrod Barnes, Gwendalyn D King, Michael Campos, Christian Faul, Matthias Salathe
Circulating levels of fibroblast growth factor (FGF) 23 are associated with systemic inflammation and increased mortality in chronic kidney disease. α-klotho, a co-receptor for FGF23, is downregulated in chronic obstructive pulmonary disease (COPD). However, whether FGF23 and klotho-mediated FGFR activation delineates a pathophysiologic mechanism in COPD remains unclear. We hypothesized that FGF23 can potentiate airway inflammation via klotho independent FGFR4 activation. FGF23 and its effect were studied using plasma and transbronchial biopsies from COPD and control patients and primary human bronchial epithelial cells isolated from COPD patients as well as a murine COPD model...
May 10, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29734515/decreased-placental-and-muscular-expression-of-the-fibroblast-growth-factor-19-in-gestational-diabetes-mellitus
#12
Dongyu Wang, Shuqia Xu, Wenjing Ding, Caixia Zhu, Songqing Deng, Xiwen Qiu, Zilian Wang
AIMS: Fibroblast growth factor (FGF) 19 has been shown to improve glycaemic homeostasis and lipid metabolism in animal models. In humans, decreased FGF19 level has been described in diabetes. This study aimed to investigate the expression of FGF19 in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Samples for measurement were obtained from 20 GDM women and 25 healthy controls. The mRNA and protein expression levels of FGF19, FGF21 and co-receptor β-klotho (KLB) in placenta, rectus muscle and subcutaneous fat tissues were quantified by real-time quantitative polymerase chain reaction, western-blot and immunohistochemistry, respectively...
May 7, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29731962/gamma-klotho-exhibits-multiple-roles-in-tumor-growth-of-human-bladder-cancer
#13
Shunta Hori, Makito Miyake, Yoshihiro Tatsumi, Yosuke Morizawa, Yasushi Nakai, Sayuri Onishi, Kenta Onishi, Kota Iida, Daisuke Gotoh, Nobumichi Tanaka, Kiyohide Fujimoto
Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29730698/klotho-preservation-by-rhein-promotes-toll-like-receptor-4-proteolysis-and-attenuates-lipopolysaccharide-induced-acute-kidney-injury
#14
Fangfang Bi, Fang Chen, Yanning Li, Ai Wei, Wangsen Cao
Renal anti-aging protein Klotho exhibits impressive properties of anti-inflammation and renal protection, however is suppressed early after renal injury, making Klotho restoration an attractive strategy of treating renal inflammatory disorders. Here, we reported that Klotho is enriched in macrophages and Klotho preservation by Rhein, an anthraquinone derived from medicinal plant rhubarb, attenuates lipopolysaccharide (LPS)-induced acute inflammation essentially via promoting toll-like receptor 4 (TLR4) degradation...
May 5, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29725301/necrostatin-1-attenuates-cisplatin-induced-nephrotoxicity-through-suppression-of-apoptosis-and-oxidative-stress-and-retains-klotho-expression
#15
Yichun Ning, Yiqin Shi, Jing Chen, Nana Song, Jieru Cai, Yi Fang, Xiaofang Yu, Jun Ji, Xiaoqiang Ding
Aim: Cisplatin is an effective chemotherapeutic drug, but the application in clinical is greatly limited by its nephrotoxicity. Necrostatin-1 (Nec-1), an inhibitor of RIP1 kinase, has been reported to inhibit RIP-mediated necroptosis. The aim of this study is to detect the protective effects of Nec-1 on the nephrotoxicity of cisplatin and to investigate its renoprotection mechanism. Methods: 8-week-old male C57BL/6 mice were randomly assigned into four groups: Control, Nec-1, Cisplatin, and Cisplatin+Nec-1...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29720929/antioxidant-effects-of-compound-walnut-oil-capsule-in-mice-aging-model-induced-by-d-galactose
#16
Huandong Zhao, Jian Li, Juan Zhao, Yang Chen, Caiping Ren, Yuxiang Chen
Background: Many plant original foods have been shown beneficial effects in humans. In the previous work, we have developed a compound capsule which contains major constituents of walnut oil and grape seed extract. Objective: To investigate the antioxidant effects of the Compound Walnut Oil Capsule (WOC) in aging model induced by D-gal. Design: 70 C57BL/6J mice were randomly divided into seven groups. Mice in normal group received daily subcutaneous injection of saline while the control group, WOC groups, Vitamin C (VC) group and pure walnut oil group received daily subcutaneous injection of D-galactose (D-gal) for 8 weeks...
2018: Food & Nutrition Research
https://www.readbyqxmd.com/read/29712948/g-395a-polymorphism-in-the-promoter-region-of-the-klotho-gene-associates-with-frailty-among-the-oldest-old
#17
Qiukui Hao, Yuting Wang, Xiang Ding, Biao Dong, Ming Yang, Birong Dong, Yuquan Wei
Frailty is characterized by a decline in physiological reserve and increased vulnerability. Previous studies have shown that KLOTHO (KL) plays a protective role in several age-related diseases. We hypothesize a probable protective effect of KL on frailty in the elderly population and included a cohort of Chinese nonagenarians and centenarians for our study. This study is part of a cross-sectional study and secondary analysis of the Project of Longevity and Aging in Dujiangyan (PLAD) study, which was conducted in Southwest China...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29701108/acute-kidney-injury-as-a-condition-of-renal-senescence
#18
Lucia Andrade, Camila E Rodrigues, Samirah A Gomes, Irene L Noronha
Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is associated with high initial mortality, morbidity, and substantial health-care costs. There is a strong connection between AKI and mechanisms of senescence activation. After ischemic or nephrotoxic insults, a wide range of pathophysiological events occur. Renal tubular cell injury is characterized by cell membrane damage, cytoskeleton disruption, and DNA degradation, leading to tubular cell death by necrosis and apoptosis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29700792/preventive-effect-of-shenkang-injection-against-high-glucose-induced-senescence-of-renal-tubular-cells
#19
Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He
Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h...
April 25, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29699061/expression-of-fibroblast-growth-factor-21-and-%C3%AE-klotho-regulates-hepatic-fibrosis-through-the-nuclear-factor-%C3%AE%C2%BAb-and-c-jun-n-terminal-kinase-pathways
#20
Kyong Joo Lee, Yoon Ok Jang, Seung-Kuy Cha, Moon Young Kim, Kyu-Sang Park, Young Woo Eom, Soon Koo Baik
Background/Aims: Fibroblast growth factor (FGF) 21 is associated with hepatic inflammation and fibrosis. However, little is known regarding the effects of inflammation and fibrosis on the β-Klotho and FGF21 pathway in the liver. Methods: Enrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and β-Klotho levels were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Furthermore, we explored the underlying mechanisms for this process by evaluating nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathway involvement in Huh-7 cells...
April 27, 2018: Gut and Liver
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