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Vitamin D AND RAS

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https://www.readbyqxmd.com/read/29067923/effect-of-vitamin-d-therapy-on-urinary-albumin-excretion-renal-functions-and-plasma-renin-among-patients-with-diabetic-nephropathy-a-randomized-double-blind-clinical-trial
#1
Plgc Liyanage, S Lekamwasam, T P Weerarathna, C Liyanage
BACKGROUND: Despite different management strategies, progression of proteinuria occurs in a sizable category of patients with diabetic nephropathy (DN). Increase in serum renin levels induced by the renin-angiotensin system (RAS) may contribute to this. Vitamin D therapy is found to have an inhibitory effect on the RAS. We aimed to study the effects of Vitamin D therapy on renal functions of patients with DN. METHODS: This was a double-blind, randomized, placebo-controlled study...
October 23, 2017: Journal of Postgraduate Medicine
https://www.readbyqxmd.com/read/29029014/1-25-dihydroxyvitamin-d-regulation-of-glutamine-synthetase-and-glutamine-metabolism-in-human-mammary-epithelial-cells
#2
Sarah Beaudin, JoEllen Welsh
Genomic profiling has identified a subset of metabolic genes that are altered by 1,25-dihydroxyvitamin D (1,25D) in breast cells including GLUL, the gene that encodes glutamine synthetase (GS). Here, we explored the relevance of vitamin D modulation of GLUL and other metabolic genes in the context of glutamine utilization and dependence. We show that exposure of breast epithelial cells to glutamine deprivation or a GS inhibitor reduced growth and these effects were exacerbated by co-treatment with 1,25D. 1,25D down-regulation of GLUL was sufficient to reduce abundance and activity of GS...
September 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/29024812/inhibition-of-pyruvate-carboxylase-by-1%C3%AE-25-dihydroxyvitamin-d-promotes-oxidative-stress-in-early-breast-cancer-progression
#3
Tomasz Wilmanski, Xuanzhu Zhou, Wei Zheng, Aparna Shinde, Shawn S Donkin, Michael Wendt, John R Burgess, Dorothy Teegarden
Maintaining reductive-oxidative (redox) balance is an essential feature in breast cancer cell survival, with cellular metabolism playing an integral role in maintaining redox balance through its supply of reduced NADPH. In the present studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized glutathione (GSH/GSSG)...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28944831/vitamin-d-alleviates-lipopolysaccharide%C3%A2-induced-acute-lung-injury-via-regulation-of-the-renin%C3%A2-angiotensin-system
#4
Jun Xu, Jialai Yang, Jian Chen, Qingli Luo, Qiu Zhang, Hong Zhang
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti‑inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)‑induced ALI...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28664839/effects-of-paricalcitol-on-biomarkers-of-inflammation-and-fibrosis-in-kidney-transplant-recipients-results-of-a-randomized-controlled-trial
#5
Manca Oblak, Gregor Mlinšek, Aljoša Kandus, Jadranka Buturović-Ponikvar, Miha Arnol
AIMS: Paricalcitol, a selective vitamin D activator, decreases proteinuria and may reduce graft failure risk in kidney transplant recipients. In this study, we evaluated the effect of paricalcitol on renin-angiotensin system (RAS) activity as well as interleukin (IL)-6 and transforming growth factor (TGF)-β plasma concentrations as biomarkers of inflammation and fibrosis. METHODS: This placebo-controlled, double-blind trial enrolled a national cohort of kidney transplant recipients with urinary protein-to-creatinine ratio (UPCR) ≥ 20 mg/mmol despite optimization of the RAS blockade...
2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28607392/chronic-vitamin-d-deficiency-induces-lung-fibrosis-through-activation-of-the-renin-angiotensin-system
#6
Yongyan Shi, Tianjing Liu, Li Yao, Yujiao Xing, Xinyi Zhao, Jianhua Fu, Xindong Xue
Pulmonary fibrosis, which influences lung function and exacerbates a patient's condition, is the ultimate stage of many lung diseases. Vitamin D deficiency is associated with pulmonary fibrosis and impaired lung function, but the underlying mechanism has not yet been fully elucidated. Moreover, vitamin D deficiency may cause over-activation of the renin-angiotensin system (RAS), which aggravates extracellular matrix (ECM) deposition and lung fibrosis. This study aims to investigate the effect of chronic vitamin D deficiency on lung fibrosis in otherwise healthy mice and to explore the role of RAS in this process...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28587403/effects-of-1-25-dihydroxyvitamin-d3-on-the-local-bone-renin-angiotensin-system-in-a-murine-model-of-glucocorticoid-induced-osteoporosis
#7
Lin Shen, Chen Ma, Bo Shuai, Yanping Yang
Active vitamin D is closely related to the circulating renin-angiotensin system (RAS) in experimental animal models and humans; however, corresponding local bone data remain limited. The present study examined whether 1,25-dihydroxyvitamin D3 supplementation altered local bone RAS elements in a murine model of glucocorticoid-induced osteoporosis (GIOP). A total of 36 8-week-old mice were randomized into three equal-sized groups: The sham, GIOP and 1,25-dihydroxyvitamin D3 treatment groups. After 12 weeks, the cancellous bone microstructure of the third lumbar vertebra and left femur from the mice from each group were examined using micro-computed tomography...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28586047/identification-and-functional-analysis-of-the-risk-micrornas-associated-with-cerebral-low-grade-glioma-prognosis
#8
Xinrui Liu, Bin Song, Shanji Li, Nan Wang, Hongfa Yang
Low-grade gliomas (LGGs) are associated with neurological disability. The present study used microRNA (miRNA) expression profiles to identify risk miRNAs for potential prognosis of cerebral LGGs. miRNA expression profiles and clinical data from 408 patients with cerebral LGGs were obtained from the Cancer Genome Atlas database. Risk miRNAs were identified by plotting Kaplan‑Meier curves and Cox proportional hazard regression analysis with the survival and KMsurv packages in R. A regulatory network of miRNA‑targets was constructed, followed by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255001/physiology-and-pathophysiology-of-the-intrarenal-renin-angiotensin-system-an-update
#9
REVIEW
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...
April 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28130181/differential-response-of-bone-and-kidney-to-acei-in-db-db-mice-a-potential-effect-of-captopril-on-accelerating-bone-loss
#10
Yan Zhang, Xiao-Li Li, Nan-Nan Sha, Bing Shu, Yong-Jian Zhao, Xin-Luan Wang, Hui-Hui Xiao, Qi Shi, Man-Sau Wong, Yong-Jun Wang
The components of renin-angiotensin system (RAS) are expressed in the kidney and bone. Kidney disease and bone injury are common complications associated with diabetes. This study aimed to investigate the effects of an angiotensin-converting enzyme inhibitor, captopril, on the kidney and bone of db/db mice. The db/db mice were orally administered by gavage with captopril for 8weeks with db/+ mice as the non-diabetic control. Serum and urine biochemistries were determined by standard colorimetric methods or ELISA...
January 24, 2017: Bone
https://www.readbyqxmd.com/read/28104492/constitutively-active-ras-signaling-reduces-1-25-dihydroxyvitamin-d-mediated-gene-transcription-in-intestinal-epithelial-cells-by-reducing-vitamin-d-receptor-expression
#11
Marsha L DeSmet, James C Fleet
High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH)2D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH)2D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene...
October 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28069388/vitamin-d-receptor-deficit-induces-activation-of-renin-angiotensin-system-via-sirt1-modulation-in-podocytes
#12
Nirupama Chandel, Kamesh Ayasolla, Hongxiu Wen, Xiqian Lan, Shabirul Haque, Moin A Saleem, Ashwani Malhotra, Pravin C Singhal
Vitamin D receptor (VDR) deficient status has been shown to be associated with the activation of renin angiotensin system (RAS). We hypothesized that lack of VDR would enhance p53 expression in podocytes through down regulation of SIRT1; the former would enhance the transcription of angiotensinogen (Agt) and angiotensinogen II type 1 receptor (AT1R) leading to the activation of RAS. Renal tissues of VDR mutant (M) mice displayed increased expression of p53, Agt, renin, and AT1R. In vitro studies, VDR knockout podocytes not only displayed up regulation p53 but also displayed enhanced expression of Agt, renin and AT1R...
February 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28033130/the-effect-of-vitamin-d-on-renin-angiotensin-system-activation-and-blood-pressure-a-randomized-control-trial
#13
RANDOMIZED CONTROLLED TRIAL
Ciaran J McMullan, Lea Borgi, Gary C Curhan, Naomi Fisher, John P Forman
OBJECTIVE: Disruption of vitamin D signaling in rodents causes activation of the rennin-angiotensin system (RAS) and development of hypertension. Observational studies in humans found lower circulating 25-hydroxyvitamin D [25(OH)D] is associated with increased RAS activity and blood pressure (BP). We performed the first randomized control trial to investigate the effects of vitamin D supplementation on the RAS in humans. METHODS: Vitamin D deficient, [25(OH)D ≤20 ng/ml), overweight individuals without hypertension were randomized into a double-blind, placebo-controlled trial of 8-weeks treatment with ergocalciferol or placebo...
April 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/27900779/mosaic-nras-q61r-mutation-in-a-child-with-giant-congenital-melanocytic-naevus-epidermal-naevus-syndrome-and-hypophosphataemic-rickets
#14
R Ramesh, N Shaw, E K Miles, B Richard, I Colmenero, C Moss
The association of hypophosphataemic rickets with verrucous epidermal naevus (EN) and elevated fibroblast growth factor 23 levels is known as cutaneous-skeletal hypophosphataemia syndrome (CSHS), and can be caused by somatic activating mutations in RAS genes. We report a unique patient with CSHS associated with giant congenital melanocytic naevus (CMN), neurocutaneous melanosis and EN syndrome, manifesting as facial linear sebaceous naevus, developmental delay and ocular dermoids. An activating mutation Q61R in the NRAS gene was found in affected skin and ocular tissue but not blood, implying that the disparate manifestations are due to a multilineage activating mutation (mosaic RASopathy)...
January 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27852823/phosphorylation-of-human-retinoid-x-receptor-%C3%AE-at-serine-260-impairs-its-subcellular-localization-receptor-interaction-nuclear-mobility-and-1%C3%AE-25-dihydroxyvitamin-d3-dependent-dna-binding-in-ras-transformed-keratinocytes
#15
Sylvester Jusu, John F Presley, Richard Kremer
Human retinoid X receptor α (hRXRα) plays a critical role in DNA binding and transcriptional activity through heterodimeric association with several members of the nuclear receptor superfamily, including the human vitamin D receptor (hVDR). We previously showed that hRXRα phosphorylation at serine 260 through the Ras-Raf-MAPK ERK1/2 activation is responsible for resistance to the growth inhibitory effects of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), the biologically active metabolite of vitamin D3 To further investigate the mechanism of this resistance, we studied intranuclear dynamics of hVDR and hRXRα-tagged constructs in living cells together with endogenous and tagged protein in fixed cells...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27591863/plasma-fat-soluble-vitamin-and-carotenoid-concentrations-after-plant-sterol-and-plant-stanol-consumption-a-meta-analysis-of-randomized-controlled-trials
#16
REVIEW
Sabine Baumgartner, Rouyanne T Ras, Elke A Trautwein, Ronald P Mensink, Jogchum Plat
PURPOSE: Plant sterols and stanols interfere with intestinal cholesterol absorption, and it has been questioned whether absorption and plasma concentrations of fat-soluble vitamins and carotenoids are also affected. We conducted a meta-analysis to assess the effects of plant sterol and stanol consumption on plasma fat-soluble vitamin and carotenoid concentrations. METHODS: Forty-one randomized controlled trials involving 3306 subjects were included. Weighted absolute and relative changes of non-standardized and total cholesterol (TC)-standardized values (expressed as summary estimates and 95 % CIs) were calculated for three fat-soluble vitamins (α- and γ-tocopherol, retinol and vitamin D) and six carotenoids (β-carotene, α-carotene, lycopene, lutein, zeaxanthin and β-cryptoxanthin) using a random effects model...
April 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/27317433/protective-effects-of-vitamin-d3-on-fimbrial-cells-exposed-to-catalytic-iron-damage
#17
Francesca Uberti, Vera Morsanuto, Debora Lattuada, Barbara Colciaghi, Andrea Cochis, Alessandro Bulfoni, Paola Colombo, Giorgio Bolis, Claudio Molinari
BACKGROUND: Recently, vitamin D3 (1alpha, 25-dihydroxyvitamin D) has shown its capability to take part in many extraskeletal functions and its serum levels have been related to patient survival rate and malignancy of many types of neoplasms, including ovarian cancers. Catalytic iron is a free circulating form of iron that is able to generate reactive oxygen species and consequently to promote a number of cellular and tissutal dysfunctions including tumorigenesis. In fertile women an important source of catalytic iron is derived from retrograde menstruation...
June 17, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27268955/targeting-inflammation-in-diabetic-kidney-disease-early-clinical-trials
#18
REVIEW
Maria Vanessa Perez-Gomez, Maria Dolores Sanchez-Niño, Ana Belen Sanz, Binbin Zheng, Catalina Martín-Cleary, Marta Ruiz-Ortega, Alberto Ortiz, Beatriz Fernandez-Fernandez
INTRODUCTION: The age-standardized death rate from diabetic kidney disease increased by 106% from 1990 to 2013, indicating that novel therapeutic approaches are needed, in addition to the renin-angiotensin system (RAS) blockers currently in use. Clinical trial results of anti-fibrotic therapy have been disappointing. However, promising anti-inflammatory drugs are currently on phase 1 and 2 randomized controlled trials. AREAS COVERED: The authors review the preclinical, phase 1 and 2 clinical trial information of drugs tested for diabetic kidney disease that directly target inflammation as a main or key mode of action...
September 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27154413/1-25-dihydroxyvitamin-d-inhibits-glutamine-metabolism-in-harvey-ras-transformed-mcf10a-human-breast-epithelial-cell
#19
Xuanzhu Zhou, Wei Zheng, G A Nagana Gowda, Daniel Raftery, Shawn S Donkin, Brian Bequette, Dorothy Teegarden
Breast cancer is the second most common cancer among women in the US. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), is proposed to inhibit cellular processes and to prevent breast cancer. The current studies investigated the effect of 1,25(OH)2D on glutamine metabolism during cancer progression employing Harvey-ras oncogene transformed MCF10A human breast epithelial cells (MCF10A-ras). Treatment with 1,25(OH)2D significantly reduced intracellular glutamine and glutamate levels measured by nuclear magnetic resonance (NMR) by 23±2% each...
October 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27041576/vitamin-d-vitamin-d-receptor-axis-regulates-dna-repair-during-oncogene-induced-senescence
#20
S Graziano, R Johnston, O Deng, J Zhang, S Gonzalo
Oncogenic Ras expression is associated with activation of the DNA damage response (DDR) pathway, as evidenced by elevated DNA damage, primarily DNA double-strand breaks (DSBs), and activation of DNA damage checkpoints, which in primary human cells leads to entry into senescence. DDR activation is viewed as a physiological barrier against uncontrolled proliferation in oncogenic Ras-expressing cells, and arises in response to genotoxic stress due to the production of reactive oxygen species that damage DNA and to hyper-replication stress...
October 13, 2016: Oncogene
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