Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Voelkl, J; Luong, TT; Tuffaha, R; Musculus, K; Auer, T; Lian, X; Daniel, C; Zickler, D; Boehme, B; Sacherer, M; Metzler, B; Kuhl, D; Gollasch, M; Amann, K; Müller, DN; Pieske, B; Lang, F; Alesutan, I.
SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling.
J Clin Invest. 2018; 128(7):3024-3040 Doi: 10.1172/JCI96477 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Co-Autor*innen der Med Uni Graz
Pieske Burkert Mathias
Sacherer Michael

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

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 vascular calcification. SGK1 promoted vascular calcification, at least partly, via NF-κB activation. Inhibition of SGK1 may, thus, reduce the burden of vascular calcification in CKD.
Find related publications in this database (using NLM MeSH Indexing)
Animals - administration & dosage
Benzamides - pharmacology
Cell Transdifferentiation - drug effects, genetics, physiology
Cells, Cultured - administration & dosage
Chondrogenesis - drug effects, genetics, physiology
Disease Models, Animal - administration & dosage
Gene Expression Regulation - administration & dosage
Humans - administration & dosage
Hydrazines - pharmacology
Immediate-Early Proteins - deficiency, genetics, metabolism
Mice - administration & dosage
Mice, Inbred C57BL - administration & dosage
Mice, Knockout - administration & dosage
Mice, Knockout, ApoE - administration & dosage
Myocytes, Smooth Muscle - drug effects, metabolism, pathology
NF-kappa B - metabolism
Osteogenesis - drug effects, genetics, physiology
Protein Kinase Inhibitors - pharmacology
Protein Serine-Threonine Kinases - deficiency, genetics, metabolism
Renal Insufficiency - metabolism, pathology
Signal Transduction - administration & dosage
Vascular Calcification - etiology, metabolism, pathology

© Med Uni Graz Impressum