SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling

Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Here, we describe that serum- and glucocorticoid-inducible kinase 1 (SGK1) was upregulated in VSMCs under calcifying conditions. In primary human aortic VSMCs, overexpression of constitutively active SGK1S422D, but not inactive SGK1K127N, upregulated osteo-/chondrogenic marker expression and activity, effects pointing to increased osteo-/chondrogenic transdifferentiation. SGK1S422D induced nuclear translocation and increased transcriptional activity of NF-κB. Silencing or pharmacological inhibition of IKK abrogated the osteoinductive effects of SGK1S422D. Genetic deficiency, silencing, and pharmacological inhibition of SGK1 dissipated phosphate-induced calcification and osteo-/chondrogenic transdifferentiation of VSMCs. Aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation in mice following cholecalciferol overload were strongly reduced by genetic knockout or pharmacological inhibition of Sgk1 by EMD638683. Similarly, Sgk1 deficiency blunted vascular calcification in apolipoprotein E–deficient mice after subtotal nephrectomy. Treatment of human aortic smooth muscle cells with serum from uremic patients induced osteo-/chondrogenic transdifferentiation, effects ameliorated by EMD638683. These observations identified SGK1 as a key regulator of vascula...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Authors: Heras Benito M, Fernández-Reyes Luis MJ Abstract Chronic kidney disease is common in people>65years of age. The development and improvement of dialysis techniques has allowed its generalisation to the entire population, when there is a situation of terminal nephropathy, without limit of use due to chronological age. Decision making in elderly patients with advanced chronic kidney disease is complex: in addition to renal parameters, both comorbidity and the presence of geriatric syndromes must be considered. This review addresses the management of information, the decision making of different trea...
Source: Medicina Clinica - Category: General Medicine Tags: Med Clin (Barc) Source Type: research
Conclusion: Diabetes was found to be a bigger cause (62.3%) of CKD than what has been reported thus far in India. At presentation association of diabetic-CKD with HT was recorded higher (78.7%) in India. Hence use of the syndrome "DHKD", (complex of diabetes, hypertension and kidney disease) is justifiable. Our study shows 54.4% of diabetic patients attending medicine OPD were uninvestigated by either physician or GP for CKD because urine albumin and serum creatinine tests were lacking. Thus, progression to CKD in many patients went unnoticed. Syndromic diagnosis of "DHKD" therefore in our view is impor...
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
In this study, we tested the hypothesis that modulation of endogenous gonadotropin-releasing hormone (Gnrh) neuronal network activity alters the mRNA expression of nuclear receptor subfamily 5 group A member 1 (Nr5a1), through one of the component of Wnt pathway signaling - catenin beta 1 (Ctnnb1) (its co-activator), and its co-repressor nuclear receptor subfamily 0, group B member 1 (Nr0b1) in the female rat pituitary gland in vivo. Adult ovariectomized rats were given a serial infusion of Gnrh, kisspeptin-10, Gnrh + Gnrh antagonist (Antide), or kisspeptin-10 + kisspeptin antagonist (kisspeptin-234) into the third ventric...
Source: Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research
PURPOSE: The aim of the current study was to evaluate the association between a decreased estimated glomerular filtration rate (eGFR) and accidental falling in elderly patients who visited the day clinic of the department of geriatric medicine of the Unive...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Elder Adults Source Type: news
The incidence of chronic kidney disease (CKD) has reached pandemic proportions across the world. Occlusive arterial disease causing critical limb ischemia and sepsis in the CKD patient is a huge clinical challenge often culminating in major amputation or mortality. Successful revascularization of these patients is challenging with added limitations due to impaired renal function, difficulties in contrast-enhanced imaging, heavily calcified arteries, and overall comorbid status.
Source: Journal of Vascular Surgery - Category: Surgery Authors: Source Type: research
Traditional contrast media are problematic in advanced chronic kidney disease. Ultrasmall superparamagnetic particles of iron oxide (ferumoxytol) are safe in chronic kidney disease and have been used for imaging in other settings. We tested the feasibility of ferumoxytol-enhanced magnetic resonance angiography (FeMRA) in patients with renal failure and performed a dose-finding study.
Source: Journal of Vascular Surgery - Category: Surgery Authors: Source Type: research
We report a specific contrast medium-free approach to patients with abdominal aortic disease and moderate to severe renal insufficiency. The protocol includes accurate assessment of chronic kidney disease (CKD), preoperative ultrasound evaluation, intravascular ultrasound, and AFX2 endoprosthesis (Endologix, Irvine, Calif).
Source: Journal of Vascular Surgery - Category: Surgery Authors: Source Type: research
Radiocephalic arteriovenous fistula (RCAVF) is the “gold standard” vascular access for end-stage chronic kidney disease patients. Exercises after AVF creation improve maturation. No articles regarding neuromuscular electrostimulation (NMES) in AVF maturation have been published.
Source: Journal of Vascular Surgery - Category: Surgery Authors: Source Type: research
In conclusion CKD results in the cerebral tissue activation of inflammatory and oxidative pathways, inhibition of antioxidant and cytoprotective system and erosion of cerebral capillary junctional complex, events that contribute to CNS dysfunction and impaired blood brain barrier. PMID: 30093950 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Authors: Jing W, Vaziri ND, Nunes A, Suematsu Y, Farzaneh T, Khazaeli M, Moradi H Abstract Progressive deterioration of kidney function in chronic kidney disease (CKD) is mediated by hypertension, oxidative stress, inflammation, and fibrosis. Renin-angiotensin blockade is commonly used to retard CKD progression. In addition, vasoactive peptides have been shown to reduce blood pressure and exert antioxidant, anti-inflammatory and anti-fibrotic effects. We hypothesized that administration of LCZ696 (sacubitril/valsartan) is more effective than valsartan alone in slowing progression of CKD. Male Sprague Dawley rats un...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
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