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https://www.readbyqxmd.com/read/28929120/sulodexide-protects-renal-tubular-epithelial-cells-from-oxidative-stress-induced-injury-via-upregulating-klotho-expression-at-an-early-stage-of-diabetic-kidney-disease
#1
Yu Ning Liu, Jingwei Zhou, Tingting Li, Jing Wu, Shu Hua Xie, Hua-Feng Liu, Zhangsuo Liu, Tae Sun Park, Yaoxian Wang, Wei Jing Liu
The hypoalbuminuric effect of sulodexide (SDX) on diabetic kidney disease (DKD) was suggested by some clinical trials but was denied by the Collaborative Study Group. In this study, the diabetic rats were treated with SDX either from week 0 to 24 or from week 13 to 24. We found that 24-week treatment significantly decreased the urinary protein and HAVCR1 excretion, inhibited the interstitial expansion, and downregulated the renal cell apoptosis and interstitial fibrosis. Renoprotection was also associated with a reduction in renocortical/urinary oxidative activity and the normalization of renal klotho expression...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28924605/pai-1-is-a-critical-regulator-of-fgf23-homeostasis
#2
Mesut Eren, Aaron T Place, Paul M Thomas, Panagiotis Flevaris, Toshio Miyata, Douglas E Vaughan
Elevated levels of fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, are associated with a number of pathologic conditions including chronic kidney disease, cardiac hypertrophy, and congestive heart failure. Currently, there are no specific treatments available to lower plasma FGF23 levels. We have recently reported that genetic plasminogen activator inhibitor-1 (PAI-1) deficiency provided a significant reduction in circulating FGF23 levels while simultaneously prolonging the life span of Klotho-deficient mice...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28919046/fgf23-activates-injury-primed-renal-fibroblasts-via-fgfr4-dependent-signalling-and-enhancement-of-tgf-%C3%AE-autoinduction
#3
Edward R Smith, Stephen G Holt, Tim D Hewitson
Bone-derived fibroblast growth factor 23 (FGF23) is an important endocrine regulator of mineral homeostasis with effects transduced by cognate FGF receptor (FGFR)1-α-Klotho complexes. Circulating FGF23 levels rise precipitously in patients with kidney disease and portend to worse renal and cardiovascular outcomes. De novo expression of FGF23 has been found in the heart and kidney following injury but its significance remains unclear. Studies showing that exposure to chronically high FGF23 concentrations activates hypertrophic gene programmes in the cardiomyocyte, has spawned intense interest in other pathological off-target effects of FGF23 excess...
September 14, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28912623/measurement-of-serum-klotho-in-systemic-sclerosis
#4
Rossella Talotta, Sara Bongiovanni, Teresa Letizia, Federica Rigamonti, Maria Chiara Ditto, Fabiola Atzeni, Fausto Salaffi, Alberto Batticciotto, Maria Chiara Gerardi, Marco Antivalle, Tarcisio Vago, Maurizio Benucci, Piercarlo Sarzi-Puttini
BACKGROUND: The aim of our study was to evaluate the serum concentration of klotho in a cohort of systemic sclerosis (SSc) patients compared to that of healthy controls and to correlate its levels with the degree and the kind of organ involvement. METHODS: Blood samples obtained from both patients and controls were collected and analysed by an ELISA test for the determination of human soluble klotho. Scleroderma patients were evaluated for disease activity through clinical, laboratory, and instrumental assessment...
2017: Disease Markers
https://www.readbyqxmd.com/read/28902627/serum-%C3%AE-klotho-levels-are-not-informative-for-the-evaluation-of-growth-hormone-secretion-in-short-children
#5
Cristina Meazza, Heba H Elsedfy, Randa I Khalaf, Fiorenzo Lupi, Sara Pagani, Mohamed El Kholy, Carmine Tinelli, Giorgio Radetti, Mauro Bozzola
BACKGROUND: α-Klotho is a transmembrane protein that can be cleaved and act as a circulating hormone (s-klotho). s-Klotho serum levels seem to reflect growth hormone (GH) secretory status. We investigated the role of s-klotho as a reliable marker of GH secretion in short children and the factors influencing its secretion. METHODS: We enrolled 40 short Egyptian children (20 GH deficiency [GHD] and 20 idiopathic short stature [ISS]). They underwent a pegvisomant-primed insulin tolerance test (ITT) and were accordingly reclassified as 16 GHD and 24 ISS...
September 13, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28901272/disorders-of-mechanisms-of-calcium-metabolism-control-as-potential-risk-factors-of-prostate-cancer
#6
Dorota Skrajnowska, Barbara Bobrowska-Korczak, Andrzej Tokarz
Prostate cancer significantly affects the overall morbidity and mortality of malignant tumours in highly developed countries. Important risk factors include family predisposition and regional, racial and dietary determinants. The scientific literature contains a great deal of data on the role of calcium and dairy products in general in the process of neoplastic transformation of the prostate. This is most likely linked to the fact that changes in the concentration of calcium ions control such varied life processes as secretion of hormones and neurotransmitters, the level of cyclic nucleotides, and cell growth, division and differentiation...
September 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28900153/genetic-ablation-of-fgf23-or-klotho-does-not-modulate-experimental-heart-hypertrophy-induced-by-pressure-overload
#7
Svetlana Slavic, Kristopher Ford, Magalie Modert, Amarela Becirovic, Stephan Handschuh, Andreas Baierl, Nejla Katica, Ute Zeitz, Reinhold G Erben, Olena Andrukhova
Left ventricular hypertrophy (LVH) ultimately leads to heart failure in conditions of increased cardiac pre- or afterload. The bone-derived phosphaturic and sodium-conserving hormone fibroblast growth factor-23 (FGF23) and its co-receptor Klotho have been implicated in the development of uremic LVH. Using transverse aortic constriction (TAC) in gene-targeted mouse models, we examine the role of Fgf23 and Klotho in cardiac hypertrophy and dysfunction induced by pressure overload. TAC profoundly increases serum intact Fgf23 due to increased cardiac and bony Fgf23 transcription and downregulation of Fgf23 cleavage...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28895643/thyroid-hormone-induced-expression-of-the-hepatic-scaffold-proteins-sestrin2-%C3%AE-klotho-and-frs2%C3%AE-in-relation-to-fgf21-ampk-signaling
#8
Luis A Videla, Romina Vargas, Barbara Riquelme, Javier Fernández, Virginia Fernández
Thyroid hormone (3,3',5-triiodothyronine, T3) accelerates energy metabolism in the liver through mechanisms involving upregulation of AMP-activated protein kinase (AMPK). This study aims to assess the influence of T3 on the expression of the scaffold proteins β-Klotho, fibroblast growth factor receptor substrate 2α (FRS2α), and Sestrin2 in relation to FGF21-AMPK signaling. Male Sprague-Dawley rats were given 0.1 mg T3/kg or hormone vehicle (controls) and studies were done 24 h after treatment. These include measurements of the mRNA expression (qPCR) of hepatic β-Klotho, FGF21, FGF21 receptor-1 (FGFR1), extracellular-signal-regulated kinase 1/2 (ERK1/2), FRS2α, ribosomal S6 kinase-1 (RSK1), liver kinase B1 (LKB1), AMPK, and Sestrin2...
September 11, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28886439/chronic-high-sucrose-diet-increases-fibroblast-growth-factor-21-production-and-energy-expenditure-in-mice
#9
Ryuya Maekawa, Yusuke Seino, Hidetada Ogata, Masatoshi Murase, Atsushi Iida, Kaori Hosokawa, Erina Joo, Norio Harada, Shin Tsunekawa, Yoji Hamada, Yutaka Oiso, Nobuya Inagaki, Yoshitaka Hayashi, Hiroshi Arima
Excess carbohydrate intake causes obesity in humans. On the other hand, acute administration of fructose, glucose or sucrose in experimental animals has been shown to increase the plasma concentration of anti-obesity hormones such as glucagon-like peptide 1 (GLP-1) and Fibroblast growth factor 21 (FGF21), which contribute to reducing body weight. However, the secretion and action of GLP-1 and FGF21 in mice chronically fed a high-sucrose diet has not been investigated. To address the role of anti-obesity hormones in response to increased sucrose intake, we analyzed mice fed a high-sucrose diet, a high-starch diet or a normal diet for 15 weeks...
July 25, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28885690/global-analysis-of-gene-expression-profiles-in-the-submandibular-salivary-gland-of-klotho-knockout-mice
#10
Sung-Min Kwon, Soo-A Kim, Jung-Hoon Yoon, Jong-In Yook, Sang-Gun Ahn
Salivary dysfunction commonly occurs in many older adults and is considered a physiological phenomenon. However, the genetic changes in salivary glands during aging have not been characterized. The present study analyzed the gene expression profile in salivary glands from accelerated aging klotho deficient mice (klotho -/-, 4 weeks old). Microarray analysis showed that 195 genes were differentially expressed (z-score > 2 in two independent arrays) in klotho null mice compared to wild-type mice. Importantly, alpha2-Na(+) /K(+) -ATPase (Atp1a2), Ca(2+) -ATPase (Atp2a1), epidermal growth factor (EGF), and nerve growth factor (NGF), which have been suggested to be regulators of submandibular salivary gland function, were significantly decreased...
September 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28883534/biological-effects-of-dosing-aerobic-exercise-and-neuromuscular-electrical-stimulation-in-rats
#11
Stefania Dalise, Loredana Cavalli, Harmanvir Ghuman, Brendon Wahlberg, Madeline Gerwig, Carmelo Chisari, Fabrisia Ambrosio, Michel Modo
Aerobic exercise (AE) and non-aerobic neuromuscular electric stimulation (NMES) are common interventions used in physical therapy. We explored the dose-dependency (low, medium, high) of these interventions on biochemical factors, such as brain derived neurotrophic growth factor (BDNF), vascular endothelial growth factor-A (VEGF-A), insulin-like growth factor-1 (IGF-1) and Klotho, in the blood and brain of normal rats, as well as a treadmill-based maximum capacity test (MCT). A medium dose of AE produced the most improvement in MCT with dose-dependent changes in Klotho in the blood...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870151/progression-of-arterial-stiffness-is-associated-with-changes-in-bone-mineral-markers-in-advanced-ckd
#12
Rathika Krishnasamy, Sven-Jean Tan, Carmel M Hawley, David W Johnson, Tony Stanton, Kevin Lee, David W Mudge, Scott Campbell, Grahame J Elder, Nigel D Toussaint, Nicole M Isbel
BACKGROUND: Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). METHODS: In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m)...
September 4, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28844880/the-fgf21-ccl11-axis-mediates-beiging-of-white-adipose-tissues-by-coupling-sympathetic-nervous-system-to-type-2-immunity
#13
Zhe Huang, Ling Zhong, Jimmy Tsz Hang Lee, Jialiang Zhang, Donghai Wu, Leiluo Geng, Yu Wang, Chi-Ming Wong, Aimin Xu
Type 2 cytokines are important signals triggering biogenesis of thermogenic beige adipocytes in white adipose tissue (WAT) during cold acclimation. However, how cold activates type 2 immunity in WAT remains obscure. Here we show that cold-induced type 2 immune responses and beiging in subcutaneous WAT (scWAT) are abrogated in mice with adipose-selective ablation of FGF21 or its co-receptor β-Klotho, whereas such impairments are reversed by replenishment with chemokine CCL11. Mechanistically, FGF21 acts on adipocytes in an autocrine manner to promote the expression and secretion of CCL11 via activation of ERK1/2, which drives recruitment of eosinophils into scWAT, leading to increases in accumulation of M2 macrophages, and proliferation and commitment of adipocyte precursors into beige adipocytes...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28844316/identifying-early-pathogenic-events-during-vascular-calcification-in-uremic-rats
#14
Luis Hortells, Cecilia Sosa, Natalia Guillén, Susana Lucea, Ángel Millán, Víctor Sorribas
Vascular calcification in chronic kidney disease is a very complex process traditionally explained in multifactorial terms. Here we sought to clarify relevance of the diverse agents acting on vascular calcification in uremic rats and distinguish between initiating and complicating factors. After 5/6 nephrectomy, rats were fed a 1.2% phosphorus diet and analyzed at different time points. The earliest changes observed in the aortic wall were noticed 11 weeks after nephrectomy: increased Wnt inhibitor Dkk1 mRNA expression and tissue non-specific alkaline phosphatase (TNAP) expression and activity...
August 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28843411/the-activin-receptor-is-stimulated-in-the-skeleton-vasculature-heart-and-kidney-during-chronic-kidney-disease
#15
Matthew J Williams, Toshifumi Sugatani, Olga A Agapova, Yifu Fang, Joseph P Gaut, Marie-Claude Faugere, Hartmut H Malluche, Keith A Hruska
We examined activin receptor type IIA (ActRIIA) activation in chronic kidney disease (CKD) by signal analysis and inhibition in mice with Alport syndrome using the ActRIIA ligand trap RAP-011 initiated in 75-day-old Alport mice. At 200 days of age, there was severe CKD and associated Mineral and Bone Disorder (CKD-MBD), consisting of osteodystrophy, vascular calcification, cardiac hypertrophy, hyperphosphatemia, hyperparathyroidism, elevated FGF23, and reduced klotho. The CKD-induced bone resorption and osteoblast dysfunction was reversed, and bone formation was increased by RAP-011...
August 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28837861/klotho-regulates-postnatal-neurogenesis-and-protects-against-age-related-spatial-memory-loss
#16
Ann M Laszczyk, Stephanie Fox-Quick, Hai T Vo, Dailey Nettles, Phyllis C Pugh, Linda Overstreet-Wadiche, Gwendalyn D King
Although the absence of the age-regulating klotho protein causes klotho-deficient mice to rapidly develop cognitive impairment and increasing klotho enhances hippocampal-dependent memory, the cellular effects of klotho that mediate hippocampal-dependent memory function are unknown. Here, we show premature aging of the klotho-deficient hippocampal neurogenic niche as evidenced by reduced numbers of neural stem cells, decreased proliferation, and impaired maturation of immature neurons. Klotho-deficient neurospheres show reduced proliferation and size that is rescued by supplementation with shed klotho protein...
July 29, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28834363/decreased-expression-of-thrombomodulin-in-endothelial-cells-by-fibroblast-growth-factor-23-%C3%AE-klotho
#17
Kenji Tanaka, Tancharoen Salunya, Yoshihiro Motomiya, Yasuki Motomiya, Yoko Oyama, Munekazu Yamakuchi, Ikuro Maruyama
Chronic kidney disease (CKD) has been known to be a state of excessive fibroblast growth factor-23 (FGF23) and α-Klotho deficiency. Patients undergoing hemodialysis have an increased mortality risk associated with cardiovascular disease and endothelial dysfunction. The mechanism responsible for the relationship of FGF23 to endothelial damage in these patients has been unclear. On the other hands, increasing evidences have demonstrated that thrombomodulin (TM) plays an important role in the endothelial barrier...
August 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28831601/endothelin-1-%C3%AE-klotho-25-oh-vit-d-levels-and-severity-of-disease-in-scleroderma-patients
#18
Mehrzad Hajialilo, Parisa Noorabadi, Sepideh Tahsini Tekantapeh, Aida Malek Mahdavi
Considering the role of endothelin-1 (ET-1) in tissue remodeling and fibrosis during the development of scleroderma as well as the effect of α-Klotho in pathogenesis of calcinosis and/or endothelial cell injury and its correlation with severity of disease, this study aimed to evaluate serum ET-1, α-Klotho and 25(OH) vitamin D levels in patients with limited and diffuse scleroderma compared to healthy subjects. In this cross-sectional study, 60 scleroderma patients according to the ACR/EULAR 2013 criteria and 60 age- and sex-matched healthy controls were included...
August 22, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28825598/peripherally-derived-fgf21-promotes-remyelination-in-the-central-nervous-system
#19
Mariko Kuroda, Rieko Muramatsu, Noriko Maedera, Yoshihisa Koyama, Machika Hamaguchi, Harutoshi Fujimura, Mari Yoshida, Morichika Konishi, Nobuyuki Itoh, Hideki Mochizuki, Toshihide Yamashita
Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with β-klotho, an essential coreceptor of FGF21...
August 21, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28812223/prognostic-potential-of-klotho-and-sfrp1-promoter-methylation-in-head-and-neck-squamous-cell-carcinoma
#20
Abeer A Alsofyani, Rawiah A Alsiary, Alaa Samkari, Baraa T Alhaj-Hussain, Jalaluddin Azam Khan, Jaudah Al-Maghrabi, Aisha Elaimi, Mohammed H Al-Qahtani, Adel M Abuzenadah, Ashraf Dallol
Hypermethylation in the CpG island promoter regions of tumor suppressors is known to play a significant role in the development of HNSCC and the detection of which can aid the classification and prognosis of HNSCC. This study aims to profile the methylation patterns in a panel of key genes including CDKN2A, CDKN2B, KLOTHO (KL), RASSF1A, RARB, SLIT2, and SFRP1, in a group of HNSCC samples from Saudi Arabia. The extent of methylation in these genes is determined using the MethyLight assay and correlated with known clinicopathological parameters in our samples of 156 formalin-fixed and paraffin-embedded HNSCC tissues...
August 16, 2017: Journal of Applied Genetics
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