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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CONCLUSION: TSLP regulated eotaxin-1 production in HNECs via JAK1/2-STAT3 signaling, which might contribute to the eosinophilic inflammation of eCRSwNP. PMID: 29911210 [PubMed - as supplied by publisher]
Source: Rhinology - Category: ENT & OMF Tags: Rhinology Source Type: research
Journal of Chemical Theory and ComputationDOI: 10.1021/acs.jctc.8b00150
Source: Journal of Chemical Theory and Computation - Category: Chemistry Authors: Source Type: research
Changes in DNA methylation are among the best-documented epigenetic alterations accompanying organismal aging. However, whether and how altered DNA methylation is causally involved in aging have remained elusive. GADD45α (growth arrest and DNA damage protein 45A) and ING1 (inhibitor of growth family member 1) are adapter proteins for site-specific demethylation by TET (ten-eleven translocation) methylcytosine dioxygenases. Here we show that Gadd45a/Ing1 double-knockout mice display segmental progeria and phenocopy impaired energy homeostasis and lipodystrophy characteristic of Cebp (CCAAT/enhancer-binding protein) mu...
Source: Genes and Development - Category: Genetics & Stem Cells Authors: Tags: Research Papers Source Type: research
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research
Publication date: Available online 18 June 2018 Source:Pharmacological Research Author(s): Carlos Alfredo Silva-Islas, Perla D. Maldonado Nuclear Factor Erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of genes involved in the metabolism, immune response, cellular proliferation, and other processes; however, the attention has been focused on the study of its ability to induce the expression of proteins involved in the antioxidant defense. Nrf2 is mainly regulated by Kelch-like ECH-associated protein 1 (Keap1), an adapter substrate of Cullin 3 (Cul3) ubiquitin E3 ligase complex. K...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 19 June 2018 Source:American Journal of Kidney Diseases Author(s): Raymond R. Townsend This narrative review summarizes a decade of experience examining the cross-sectional and longitudinal relationships of arterial stiffness, as assessed using carotid-femoral pulse wave velocity, with outcomes in patients with chronic kidney disease enrolled in the Chronic Renal Insufficiency Cohort. Our goal is to review the importance of the pulse wave contour and pulse wave velocity and present data on the reproducibility of pulse wave velocity measurements, determinants of pulse wave velocity, and t...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
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Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research
AbstractBackgroundPerioperative care has been identified as an area of wide variability in quality, with conflicting models, and involving multiple specialties. In 2014, the Loma Linda University Departments of Anesthesiology and Urology implemented a perioperative hospitalist service (PHS), consisting of anesthesiology-trained physicians, to co-manage patients for the entirety of their perioperative period. We hypothesized that implementation of this PHS model would result in an improvement in patient recovery.MethodsAs a quality improvement (QI) initiative, the PHS service was formed of selected anesthesiologists who rec...
Source: Perioperative Medicine - Category: Surgery Source Type: research
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Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
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